COLUMBIA  LIBRARIES  OFFSITE 

HEALTH  SCIENCES  STANDARD 


lllllllll 

■HX64088014 

QP195.R11  studies  in  pancreati 


RECAP 


aFids         nil 

Columbia  2Bntt)er£^ttp 

inti)f(£ttpcflfttitork 

College  of  l^\)v^\tmn^  ani)  burgeons 


i^ibrarp 


Digitized  by  tine  Internet  Arciiive 

in  2010  witii  funding  from 

Open  Knowledge  Commons  (for  the  Medical  Heritage  Library  project) 


http://www.archive.org/details/studiesinpancreaOOrach 


STUDIES  IN 


PANCREATIC 
DIGESTION 


RACHFORD. 


COLUMBIA  UNIVFRSITY 

DEPARTMENT  OF  PHYSIOLOGY 

College  of  Physicians  and  Surgeons 
437  west  fifty  ninth  stueet 

NEW   YOfiK 


MDCCCC 


STUDIES  IN 


PANCREATIC  DIGESTION 


MADE  WITH  PANCREATIC  JUICE. 


BY 

B.  K.  RACHFORD,  M.D., 

PROFESSOR   OF    THERAPEUTICS,  MEDICAL    COLLEGE    OF    OHIO;    PEDIATRIST    TO    CINCINNATI 

AND    GOOD    SAMARITAN    HOSPITALS;     MEMBER    OF    ASSOCIATION    OF 

AMERICAN     PHYSICIANS    AND     AMERICAN 

PEDIATRIC    SOCIETY,  ETC. 


CINCINNATI  : 

CINCINNATI  LANCET  PRESS, 
1900. 


:> 


PREFACE. 


This  book  is  ii  reprint  of  a  series  of  research  articles  origi- 
nally printed  in  various  medical  journals. 

These  studies  were  made  with  rabbits'  pancreatic  juice,  and 
the  conclusions  here  presented  differ  somewhat  from  those  arrived 
at  by  other  investigators,  working  with  pancreatic  extracts. 

Since  these  differences  of  opinion  exist,  I  have  thought  best 
to  reproduce  these  papers  in  a  convenient  form,  that  they  may 
be  more  accessible  to  students  of  intestinal  digestion. 


CONTENTS. 


I — Influence  of  Bile  on  the  Fat-Splitting  Properties 
OF  Pancreatic  Juice. 

II — Fat  Digestion. 

Ill — The  Diastatic  Action  of  Pancreatic  Juice. 

IV — Influence   of   Bile,    ov   Acids,    and   of   Alkalies   ox 
THE  Proteolytic  Action  of  Pancreatic  Juice. 

\' — Pancreatic  Digestion  From  the  Standpoint  of  the 
Comparative  Anatomy  of  the  Bile  and  Pan- 
creatic Ducts  in  Mammals. 

VI — Pancreatic  Digestion  of  Casein. 


Reprinted  from  the  Journal  of  Physiology,   Vol.  XII,  No.  1,  1891. 


L— INFLUENCE  OF  BILE  ON  THE  FAT- SPLITTING 
PROPERTIES  OF  PANCREATIC  JUICE. 


In  the  spring  and  summer  of  last  year,  in  the  Berlin  Physio- 
logical Laboratory,  I  made  a  study  of  the  fat-splitting  properties 
of  pancreatic  juice  and  read  a  paper  on  this  subject  before  the 
physiological  section  of  the  Tenth  International  Medical  Con- 
gress. The  complete  and  more  detailed  presentation  of  this 
work  is  the  object  of  this  paper. 

The  short  paper  on  emulsion,  apart  from  any  interest  or  value 
that  may  attach  to  this  portion  of  the  paper  itself,  is  of  import- 
ance because  of  its  bearing  on  the  methods  used  in  the  study  of 
pancreatic  juice. 

EMULSIONS. 

In  1870  E.  V.  Brucke^  announced  the  fact  that  when  rancid 
oiP  is  shaken  with  a  solution  of  sodium  carbonate  and  certain 
other  alkaline  fluids  an  immediate  emulsion  results.  He  believed 
that  the  oil  was  broken  into  fine  globules  by  the  shaking  and  that 
the  soap  formed  served  to  hold  the  emulsion  by  preventing  the 
union  of  the  oil  globules. 

In  1878  Johannes  Gad^  called  attention  to  the  fact  that  when 
oil  containing  the  proper  percentage  of  fatty  acid  was  placed  on 
the  surface  of  a  carbonate  of  sodium  solution  a  beautiful  spon- 
taneous emulsion  resulted,  and  from  this  he  held  that  neither 
shaking  nor  any  other  outside  mechanical  force  was  necessary  to 
the  formation  of  an  emulsion,  but  that  the  chemical  force  devel- 
oped by  the  soap  formation  was  of  itself  sufficient  under  favor- 
able circumstances  to  break  the  oil  drops  into  the  finest  emulsion 
globules.  There  is  but  little  room  for  doubt,  I  think,  that  Gad 
is  right  in  this  opinion.      In  fact,  the  only  question  which  might 

1  Sitziingshericht  der  Wiener  Acad,  der  Wissensch.,  Bd.  Ixi,  11.  Abth., 
p.  362. 

2  By  rancid  oil  is  meant  oil  containing  fatty  acid. 

3  Archiv  f.  Anat.  u.  Physiol..  1878,  p.  181. 


8  PANCREATIC    DIGESTION. 

arise  is  whether  the  force  developed  by  the  soap  formation  is  not 
a  physical  (Quincke)  rather  than  a  chemical  one.  Gad  also 
believed  with  Brucke  that  the  soap  formed  had  much  to  do  with 
holding  the  emulsion,  and  this  proposition  is,  I  think,  now 
everywhere  accepted,  although  opinions  differ  widely  as  to  the 
manner  in  which  the  soap  acts  in  bringing  about  this  result, 

I  wish  here  to  call  attention  to  the  method  used  by  Gad  in  his 
study  of  spontaneous  emulsion,  since  this  method  is  the  basis  of 
the  methods  used  by  me  in  the  study  of  the  fat-splitting  proper- 
ties of  pancreatic  juice. 

A  \  per  cent,  carbonate  of  sodium  solution  is  placed  in  a 
series  of  watch-glasses,  and  drops  of  oil  containing  different  per- 
centages of  fatty  acid  are  gently  placed,  by  means  of  a  pipette, 
on  the  surface  of  the  fluid  in  the  watch-glasses.  The  amount  of 
spontaneous  emulsion  in  the  various  glasses  is  carefully  noted 
and  compared,  and  in  this  way  one  can  readily  ascertain  the  per- 
centage of  fatty  acid  required  to  give  the  best  emulsion. 

It  must,  of  course,  be  remembered  in  this  connection,  that  the 
percentage  of  fatty  acid  required  to  give  the  maximum  amount 
of  spontaneous  emulsion  will  vary  with  other  conditions,  such 
as  temperature,  strength  of  soda  solution,  etc.,  and  that  therefore 
only  experiments  made  under  similar  conditions  can  be  com- 
pared. By  this  method  Gad  observed  that  under  otherwise 
similar  conditions  a  certain  definite  percentage  of  fatty  acid  must 
be  present  in  oil  to  give  the  maximum  amount  of  spontaneous 
emulsion.  For  example,  he  found  that  with  a  \  per  cent,  carbon- 
ate of  sodium  solution  at  room  temperature,  about  5^^  per  cent,  of 
fatty  acid  was  required,  and  that  with  increasing  or  diminishing 
per  cents,  of  acid  above  or  below  5^  per  cent,  he  got  less  and  less 
emulsion,  until  finally  there  was  no  emulsion  at  all.  A  very  little 
more  or  less  than  5-|  per  cent,  of  acid  gave  an  incomplete  emul- 
sion. He  found,  therefore,  that  the  limits  of  good  spontaneous 
emulsibility  were  not  only  constant  but  also  quite  narrow,  and 
upon  these  important  facts  depends  the  value  of  his  method. 

We  have  in  Gad's  method  a  simple  and  accurate  means  of 
determining  the  proper  percentage  of  fatty  acids  for  giving  the 
best  spontaneous  emulsion  of  any  given  oil  under  given  con- 
ditions. 

After  repeating  the  experiments  of  Gad  and  confirming  his 
observations  I  devoted  considerable  time  to  the  study  of  the  influ- 


B.  K.  RACHFORD.  9 

ence  of  shaking  and  other  outside  mechanical  means  on  the  for- 
mation of  emulsions. 

The  oil  used  almost  exclusively  in  my  experiments  was  olive 
oil  that  had  been  neutralized  by  shaking  for  tw^o  hours  with  a 
saturated  solution  of  barium  hydrate  at  a  temperature  of  95°  C. 
and  then  pipetted  and  filtered.  Oil  freshly  prepared  in  this 
manner  will  be  found  practically  neutral,  and  the  term  neutral 
olive  oil  as  used  in  this  paper  always  refers  to  such  oil. 

The  stirring  was  done  chiefly  by  currents  of  air  carried  from 
a  blowing  machine  into  the  liquids  to  be  stirred  by  means  of 
rubber  tubing  and  glass  rods.  This  method  is  not  only  more 
convenient,  but  it  has  other  advantages  over  the  ordinary  one  of 
shaking  the  tube. 

My  experiments  led  me  to  the  following  conclusions  : 

1.  No  amount  of  stirring  will  give  a  permanent  emulsion 
of  either  neutral  olive  oil  or  of  rancid  olive  oil  in  distilled  water. 
(Frey^  found  differently.) 

2.  No  amount  of  stirring  will  give  a  permanent  emulsion  with 
neutral  olive  oil  and  a  \  per  cent,  carbonate  of  sodium  solution, 

3.  Shaking  rancid  oil  and  a  \  per  cent,  carbonate  of  sodium 
solution-  gives  a  good  permanent  emulsion,  even  though  the  oil 
contain  a  very  small  or  a  very  large  percentage  of  fatty  acid. 

From  the  above  observations  we  see  that  when  the  conditions 
for  soap  formation  are  present,  shaking  very  much  widens  the 
range  of  good  emulsibility  and  promotes  the  formation  of  a  good 
permanent  emulsion,  but  when  the  conditions  for  soap  formation 
are  not  present,  the  shaking  has  no  influence  whatever. 

In  our  study  of  emulsions  we  must  remember  that  two  things 
are  necessary  to  the  formation  of  a  good  permanent  emulsion  : 

1.  The  oil  must  be  broken  into  very  fine  globules. 

2.  These  globules  must  not  only  be  prevented  from  running 
together,  but  they  must  also  remain  rather  uniformly  distributed 
throughout  the  liquid.  Now  since  we  know  that  soap  and  cer- 
tain other  materials,  as  albumen  and  mucilage,  have  the  power  of 
holding  emulsions,  it  would  seem  an  easy  matter  to  make  a  me- 
chanical emulsion  by  shaking  neutral  oil  in  a  solution  of  soap, 
albumen  or  mucilage ;  but  such  in  truth  is  not  the  case.  In  my 
experiments  with  soap  solution  and  neutral  olive  oil  I  found  that 
in  very  heavy  solutions  of  soap,  by  violent  and  prolonged  stirring, 

I   Archiv  f.  Ai?af.  11.  PJiysioL.  1S81,  p.  382. 


lo  PANCREATIC    DIGESriON. 

I  could  get  only  an  imperfect  emulsion,  one  in  which  the  oil 
globules  were  larger  and  more  variable  in  size  than  those  formed 
by  spontaneous  emulsion. 

These  mechanical  emulsions  do  not  approach  in  perfection'  a 
physiological  emulsion,  such  as  milk  ;  and  they  can  be  formed 
only  in  very  viscous  liquids  and  with  such  great  mechanical  force 
as  to  place  them  beyond  the  pale  of  physiological  importance. 

For  the  study,  therefore,  of  the  influence  of  stirring  in  the 
formation  of  good  permanent  emulsions,  such  as  may  have  some 
physiological  importance,  ^ve  must  return  to  the  experiments 
already  noted,  where  a  moderate  amount  of  stirring  very  much 
hastened  and  promoted  the  formation  of  good  emulsions  when 
the  conditions  for  soap  formation  were  present. 

The  influence  of  stirring  under  such  circumstances  may,  I 
think,  be  explained  as  follows.  When  too  little  acid  is  present 
for  the  formation  of  a  good  spontaneous  emulsion,  the  shaking 
or  stirring  simply  favors  the  emulsion  by  promoting  soap  forma- 
tion. It  breaks  the  oil  into  a  number  of  small  globules  which 
are  constantly  presenting  new  surfaces  to  the  surrounding  alka- 
line fluid,  thus  enabling  the  soda  to  combine  with  all  the  fatty 
acid  present,  in  the  formation  of  soap,  and  the  chemical  force 
thus  liberated  by  the  soap  formation  becomes  an  important  factor 
in  the  breaking  of  the  oil  drops  into  the  fine  emulsion  globules, 
just  as  it  does  in  pure  spontaneous  emulsion. 

When  too  much  acid  is  present  for  good  spontaneous  emulsion, 
the  process  is  brought  to  a  stand-still  by  the  formation  of  a  heavy 
soap  membrane  between  the  oil  drop  and  the  alkaline  fluid,  thus 
preventing  further  soap  formation.  Under  these  conditions, 
shaking  breaks  the  oil  drop  and  consequently  the  soap  membrane, 
thus  constantly  presenting  new  surfaces  of  oil  to  the  surrounding 
alkaline  fluid  and  in  that  way  favoring  soap  formation  and  the 
resulting  emulsification.  We  see,  therefore,  that  while  shaking 
may  play  a  very  important  role  in  the  formation  of  emulsions, 
its  action  is  chiefly  an  indirect  one,  promoting  emulsification  by 
favoring  soap  formation,  and  that  the  chemical  force  liberated 
by  this  process  is  the  force  most  active  in  breaking  the  oil  drops 
into  fine  emulsion  globules.  From  my  experiments  I  formulate 
the  following  general  law  concerning  the  influence  of  stirring  in 
the  formation  of  emulsions. 

The   amount  of  stirring  required  to   give   a  good  emulsion  of 


B.  K.  RACHFORD.  ii 

oil  in  a  \  per  cent,  carbonate  of  sodium  solution  will  be  in  inverse 
proportion  to  the  nearness  with  which  the  percentage  of  fatty  acid 
in  the  oil  approaches  the  proper  percentage  for  giving  the  maxi- 
mum amount  of  spontaneous  emulsion.  If  the  oil  contains  the 
exact  percentage  of  fatty  acid  for  giving  the  best  spontaneous 
emulsion,  then  the  shaking  will  be  superfluous,  since  a  good 
emulsion  will  form  without  motion  and  no  amount  of  shaking 
can  improve  it.  If,  on  the  other  hand,  the  oil  be  entirely  free 
from  fatty  acid,  then,  as  we  have  seen,  no  amount  of  shaking 
will  give  a  good  emulsion.  Between  these  two  extremes  the 
above  law  applies,  and  shaking  may  contribute  very  largely  to 
the  formation  of  emulsions. 

In  the  application  of  the  above  principles  we  have  a  simple 
and  convenient  method  of  determining  when  an  oil  is  practically 
free  frorn  fatty  acid;  viz.,  shake  it  with  a  \  per  cent,  solution  of 
carbonate  of  sodium,  and  if  there  be  no  fatty  acid  present,  the 
mixture  rapidly  clears. 

By  the  same  method  we  may  tell  when  we  have  fatty  acid 
free  from  admixture  with  oil;  viz.,  shake  the  fatty  acid  with  the 
soda  solution,  and  if  oil  be  present  we  will  have  more  or  less 
milkv  whiteness,  which  is  characteristic  of  emulsions ;  but  if  no 
oil  be  present,  we  will  have  a  simple  cloudiness  due  to  the  insol- 
uble soap  formed.  From  all  that  has  been  said,  it  follows  as  a 
logical  conclusion  that  the  energy  required  to  make  an  oil  emul- 
sible  will  be  in  direct  proportion  to  the  stability  of  the  oil  mole- 
cule of  the  given  oil.  The  more  stable  the  oil  molecule,  the  more 
energy  required  to  split  it  into  fatty  acid  and  glycerine.  It  mat- 
ters not  whether  the  energy  be  in  the  form  of  heat  or  of  organized 
ferments,  bacteria,  or  of  unorganized  ferments,  as  the  fat-splitting 
ferment  of  the  pancreas. 

During  my  experiments  I  found  that  heating  neutral  olive  oil 
developed  fatty  acid  and  made  it  emulsible,  and  that  if  this  heated 
oil  be  again  neutralized  it  became  non-emulsible,  thus  showing 
the  emulsibility  to  be  due  to  the  acidity.  I  also  found  that  the 
greater  the  heat  and  the  longer  applied,  the  more  fatty  acid  was 
developed,  so  that  boiled  olive  oil  contained  too  much  acid  for 
good  spontaneous  emulsibility. 

It  is  an  interesting  fact  that  the  acids  freed  by  heating  various 
oils  seemed  to  have  greater  power  in  making  them  emulsible 
than  a  like  quantity  of  oleic  acid.   This  is  especially  true  of  castor 


12  PANCREATIC    DIGESTION. 

oil.  Castor  oil  is  not  made  more  emulsible  by  the  addition  of 
oleic  acid,  but  after  boiling  it  may  be  emulsified  by  shaking  it 
with  sodium  solution,  but  it  never  becomes  spontaneously  emul- 
sible ;  this  latter  fact  Gad  called  attention  to  and  thought  it  due 
to  the  viscosity  of  this  oil.  The  stability  of  the  castor  oil  mole- 
cule is  shown  by  the  great  heat  required  to  develop  sufficient 
fatty  acid  to  give  an  emulsion.  These  facts  seem  to  indicate  that 
the  fatty  acids  of  an  oil  are  the  fatty  acids  best  adapted  for  giving 
emulsibility  to  this  particular  oil. 

It  is  a  physiological  fact  beyond  dispute  that  the  splitting  of 
fats  is  a  most  important  preliminary  step  in  fat  digestion.  That 
the  cooking  of  fats  will  develop  in  them  fatty  acid  is  therefore  a 
fact  of  considerable  physiological  importance,  and  one  that,  so 
far  as  I  know,  has  not  previously  been  noticed. 

As  I  have  previously  intimated,  it  is  my  belief  that  the  chemi- 
cal force  developed  by  soap  formation  is  the  chief  factor  in  the 
formation  of  all  phj'siological  emulsions,  that  it  plays  quite  as 
important  a  role  in  the  formation  of  the  emulsion  as  the  soap 
does  in  holding  it  after  it  is  formed. 

That  soap  has  the  property  of  holding  emulsions  is,  I  think, 
an  undisputed  fact,  but  the  manner  in  which  the  soap  acts  is  a 
question  concerning  which  there  has  been  much  difference  of 
opinion.  In  explanation  of  this  difficult  problem  I  wish  modestly 
to  express  my  belief  in  a  theory  of  emulsions  which  is  a  modifi- 
cation of  that  offered  by  Gad.  Gad  believed  that  the  fine  globules 
of  oil  were  coated  as  soon  as  formed  with  insoluble  soap  particles 
which  formed  a  protecting  envelope  that  prevented  the  oil  drops 
from  running  together.  The  modification  which  I  offer  is  as 
follows  :  the  cheinical  process  of  soap  formation  which  breaks 
the  oil  into  fine  globules  must  develop  considerable  heat ;  this 
must  necessarily  have  the  effect  of  bringing  a  certain  amount  of 
otherwise  insoluble  soap  into  solution.  This  heat  will  necessarily 
be  local  and  felt  chiefly  just  at  the  point  where  the  soap  is  formed, 
and  all  the  surrounding  liquid  will  be  cooler.  The  soap,-  therefore, 
which  is  brought  into  solution  by  the  heat  either  is  precipitated 
a  moment  later  on  coming  in  contact  with  cooler  parts  of  the 
liquid,  or  it  causes  increased  viscosity  in  the  liquid.  We  may 
therefore  say  that  the  heat  is  developed,  the  soap  formed  and 
dissolved  and  the  oil  broken  by  the  same  force,  in  the  same  place 
and  at  the  same  time.      By  this  mechanism  the  oil  globules  are, 


B.   K.  RACHFORD.  i^ 

as  soon  as  formed,  coated  with  a  liquid  soap  which  a  moment 
later  hardens  about  them  in  the  form  of  soap  membranes.  These 
soap  membranes  at  the  moment  of  their  formation  are  not  as 
capable  of  holding  the  globules  as  they  are  later,  when,  on  cooling, 
they  become  more  resisting.  If  this  theory  be  true,  it  would 
follow  that  an  appreciable  length  of  time  must  elapse  after  the 
formation  of  an  emulsion  before  it  reaches  its  highest  degree  of 
stability.  And  this,  in  fact,  I  find  to  be  true,  that  the  emulsions 
can  be  more  easily  destroyed  at  the  moment  of  their  formation 
than  later,  and  it  is  only  in  explanation  of  this  and  other  facts 
that  the  above  theory  is  offered.  The  following  conclusions  I 
draw  from  my  experiments,  and  some  of  them  are  best  explained 
by  this  theory. 

I.  If  bile  be  present  an  emulsion  cannot  form,  although  all 
the  conditions  otherwise  favorable  to  its  formation  be  present. 
This  fact  was  pointed  out  by  Gad,  and  he  offered  in  explanation 
that  the  soap-dissolving  properties  of  the  bile  prevented  the  for- 
mation of  insoluble  soap  membranes,  and  that  the  unprotected 
oil  globules  ran  together  and  came  to  the  surface  as  free  oil. 

2.  If  bile  is  added  to  an  emulsion,  the  moment  after  it  is 
formed  the  emulsion  rapidly  clears  by  creaming,  but  no  free  oil 
appears  on  the  surface.  Here  it  seems  that  the  soap  not  in  mem- 
branes is  dissolved.  This  increases  the  specific  gravity  and 
diminishes  the  viscosity  of  the  liquid,  and  as  a  result  the  soap- 
coated  globules  rise  to  the  surface  as  cream  ;  why  it  is  that  the 
soap  in  the  membranes  more  quickly  acquires  the  property  of 
resisting  the  solvent  action  of  bile  than  the  soap  not  in  mem- 
branes I  cannot  say,  yet  this  seems  the  only  explanation  of  the 
above  phenomenon. 

3.  If  bile  be  added  to  an  emulsion  some  minutes  after  it  has 
formed,  it  has  no  effect  in  destroying  the  emulsion.  The  above 
propositions  clearly  indicate  that  an  appreciable  length  of  time 
must  elapse  after  the  formation  of  an  emulsion  before  it  reaches 
its  highest  degree  of  stability. 

4.  One-tenth  per  cent,  nitric  and  sulphuric  acid  and  Y5 
per  cent,  lactic  acid  solutions  rapidly  destroy  emulsions,  the  free 
oil  running  to  the  surface.  Acids  destroy  emulsions  by  com- 
bining with  the  base  of  soaps  and  freeing  the  fatty  acids ;  the 
soap  being  thus  destroyed,  the  liquid  is  much  less  viscous,  while 
the   specific   gravity  is   very  little   altered.     The  oil  globules  are 


14  PANCREATIC    DIGESTION. 

therefore  driven  to  the  surface  as  cream,  but  if  the  acid  be  stronger, 
the  soap  in  membrane  is  also  destroyed,  and  free  oil  floats  on 
the  surface.  The  membrane  soap  is  here  found  to  be  more  resist- 
ing to  soap  destroyers  than  soap  not  in  membranes. 

5.  Hydrochloric  acid  has  a  much  less  destructive  influence  on 
emulsions  than  has  nitric  or  sulphuric  acid,  and  lactic  acid  has  a 
less  destructive  influence  than  acetic. 

6.  If  sapo  medicatus  ^  be  shaken  in  a  Yio  per  cent,  nitric  or 
sulphuric  acid  solution  the  soda  of  the  soap  will  combine  with 
the  nitric  or  sulphuric  acid  and  fine  globules  of  free  fatty  acid 
will  rise  to  the  surface.  Sapo  medicatus  is  more  easily  destroyed 
by  nitric  and  sulphuric  acids  than  it  is  by  hydrochloric  acid. 
These  facts  strongly  corroborate  the  opinion  that  acids  destroy 
emulsions  by  destroying  soaps. 

THE    FAT-SPLITTING    PROPERTIES    OF    PANCREATIC 
JUICE. 

Since  the  publications^  of  Claude  Bernard,  physiologists  have 
generally  believed  that  pancreatic  juice  has  the  property  of  split- 
ting neutral  fats  into  fatty  acid  and  glycerine.  Claude  Bernard 
himself  believed  that  the  pancreatic  juice  had  a  twofold  action  on 
fats.  In  the  first  place,  he  said  that  when  neutral  oil  and  pan- 
creatic juice  were  shaken  together  an  instantaneous  emulsion  re- 
sulted. In  the  second  place,  that  the  prolonged  action  of  pan- 
creatic juice  on  neutral  oil  would  develop  fatty  acid.  He  did  not 
in  any  way  associate  these  two  processes,  and  believed  them  to  be 
due  to  entirely  different  properties  of  the  juice,  the  emulsion 
being  an  instantaneous  process  and  the  fat  splitting  occurring 
only  after  considerable  time.  And  these  two  processes  are  still 
described  as  separate  and  distinct  properties  of  pancreatic  juice 
m  some  of  our  most  recent  text-books.  But  since  the  publications 
of  Brucke  and  Gad,  most  German  physiologists  have  associated 
these  processes,  believing  that  the  emulsion  was  wholly  due  to 
the  fatty  acid  which  had  been  developed  in  the  oil  by  the  fat- 
splitting  ferment,  and  that  the  pancreatic  juice  contained  no 
emulsion  ferment ;  this  opinion  was  a  matter  of  inference  from 
the   works  of  Brucke,  Gad   and   others,  rather  than   from  actual 

1  A  soda  soap  made  with  olive  oil  acids. 

2  Compt.  rend,  de  Vacad.  de  Paris.  T.  xxviii.  Arch,  general,  1849. 
Memoire  sur  le  Pancreas,  Paris,  1856. 


B.   K.   RACHFORD.  15 

experiments  with  the  juice  itself.  I  have  failed  to  find  that  any 
systematic  work  in  this  direction  had  been  done  with  pancreatic 
juice  since  the  days  of  Claude  Bernard.  Qiiite  a  number  of 
attempts  have  been  made,  but  the  difficulties  in  obtaining  a 
normal  juice  w^ere  so  great  that  no  extensive  w^ork  has  been  done 
and  no  important  fact  added  to  our  knowledge.  But  while 
almost  no  work  has  been  done  with  the  juice  itself,  an  immense 
amount  of  work  has  been  done  with  pancreatic  extracts  and 
infusions  made  from  the  gland.  Physiologists  have  seemed  to 
take  for  granted  that,  in  studying  the  physiological  properties  of 
pancreatic  juice,  the  juice  itself  offered  no  advantage  over  these 
extracts.  In  fact,  they  seemed  to  believe  from  the  great  difficulty 
in  obtaining  a  normal  juice  that  the  extracts  were  preferable,  and 
our  knowledge  of  the  present  day  is  based  almost  exclusively  on 
experiments  with  the  extracts,  and  but  for  the  fact  that  they  con- 
tain a  fat-splitting  ferment  the  time-honored  opinion  of  Claude 
Bernard  would  have  carried  but  little  weight.  For  these  reasons, 
therefore,  a  systematic  investigation  into  the  fat-splitting  proper- 
ties of  the  pancreatic  juice  seemed  to  offer  a  fertile  field  for  work. 
Although  in  the  beginning  the  obstacle  of  obtaining  normal 
juice  in  sufficient  quantities  to  prosecute  this  investigation  seemed 
insurmountable,  yet  I  was  fortunate  enough  to  hit  upon  a  method 
by  which  I  could  readily  obtain  from  the  rabbit  a  normal  juice  in 
sufficient  quantities  for  experimental  purposes.  The  operation 
for  temporary  pancreatic  fistula  in  the  rabbit  is  easily  and  quickly 
done  as  follows.  JNIake  an  abdominal  incision  in  the  linea  alba 
two  and  one-half  inches  long.  Bring  the  duodenum,  which  is 
readily  found  high  up  in  the  right  hyjDochondriac  region,  through 
this  opening,  run  down  the  gut  to  a  point  where  the  peritoneum 
binds  it  so  closely  that  it  will  not  come  through  the  opening,  and 
just  at  this  point  will  be  found  the  pancreatic  duct  as  it  runs 
through  a  leaf  of  the  pancreas  to  the  small  intestine.  Resect 
two  inches  of  the  intestine  at  this  point,  leaving  its  mesenteric 
attachment,  tie  the  cut  ends  of  the  intestine  above  and  below 
and  drop  them  in  the  cavity,  bringing  the  resected  portion  through 
the  abdominal  wound.  The  abdominal  wound  is  now  partially 
closed  by  stitches,  leaving  only  sufficient  opening  for  the  mesen- 
tery running  to  the  resected  gut.  This  resected  gut  is  now  laid 
open  opposite  the  mesenteric  attachm.ent  and  spread  out  on  the 
abdominal  wall.      The  ends  of  the  gut  are  clamped  and  its  mar- 


i6  PANCREATIC    DIGESTION. 

gins  packed  with  absorbent  cotton  to  prevent  bleeding.  Insert 
a  small  glass  cannula  through  the  pancreatic  papilla  into  the  pan- 
creatic duct  and  cover  the  exposed  mucous  membrane  with  absorb- 
ent cotton  saturated  with  common  salt  solution.  The  flow  of 
juice  begins  at  once  and  continues  from  four  to  six  hours.  In 
this  manner  about  i  c.c.  of  juice  uniform  and  powerful  in  phy- 
siological action  may  be  collected.  This  operation  is  a  modifi- 
cation of  the  Heidenhain  permanent  fistula  operation^  and  has 
the  advantage  of  being  simple  and  uniformly  successful. 

In  my  experiments  I  used  the  pancreatic  juice  of  the  rabbit,  as 
it  seemed  quite  impossible  for  me  to  obtain  from  the  dog  a  normal 
juice  in  sufiicient  quantities  for  experimentation.  The  fat  used 
was  neutral  olive  oil. 

I  worked  for   several  weeks   with  very  faulty  methods   before 
I  hit  upon   the  method  which  I  afterwards   used,  and   which,  I 
think,  is  admirably  adapted  to  the  study  of  the  fat-splitting  pro- 
perties of  pancreatic  juice.      The  foundation-stone  of  the  method 
is  the  spontaneous  emulsion  method  of  Gad.   We  have  previously 
seen  how  by  this  method  we  may  determine  when  an  oil  has  the 
proper    percentage   of  fatty   acid   to   give   the   best   spontaneous 
emulsion   under  certain   given  conditions.      After  having  estab- 
lished  the  conditions  under   which  one  can   get  a   good  emulsion 
with  a  certain   per  cent.  (5^)  of  fatty  acid,  it  is  evident  that  we 
can  use  this  method  for  determining  when  an  oil  has  this  per- 
centage of  fatty  acid,  and  since  the  completeness  of  the  sponta- 
neous emulsion  will  be  in  direct  proportion  to  the  nearness  with 
which  the  quantity  of  fatty  acid  in  the  oil  approaches  this  percent- 
age, we  have  also  a  method  of  estimating  the  amount  of  increase 
of  fatty  acid   in   any  oil  by  testing  its   spontaneous  emulsibility 
from  time  to  time.     For  example,  let  us  suppose  that  we  have  a 
neutral  oil  in   which  fatty  acid   begins   to  develop,  and  that  this 
process   slowly  continues  until   all   the  oil  is  changed   into  fatty 
acid  and  glycerine.      If  the   test  of  spontaneous  emulsibility  be 
applied  to  such  an  oil  by  placing  a  drop  of  it  from  time  to  time 
on  carbonate  of  sodium   solution,  we  get  at  first  no  emulsion  at 
all,  and  then   with  the   development  of  some   fatty  acid  a  slight 
emulsion,    then    more   and    more   with    increasing   quantities   of 
acid   until   the   maximum   emulsion    is   reached,  which  indicates 
that    about    5^    per   cent,   of    acid    has    been    developed.       The 
I   Hatidbtich  der  Physiologie,  Hermann,  Bd.  v. 


B.  K.  RACHFORD.  17 

emulsion  then  decreases  with  the  further  increase  of  acid  until 
finally  we  get  no  spontaneous  emulsion  at  all,  which  indicates- 
about  12  per  cent,  of  acid.  Beyond  this  point  the  increase 
of  acidity  cannot  be  measured  by  spontaneous  emulsion,  but  in 
this  particular  and  under  these  circumstances  the  emulsion  formed 
by  shaking  is  of  some  value,  for  good  emulsions  may  still  be  had 
in  this  way  after  too  much  acid  has  been  developed  for  sponta- 
neous emulsion.  But  the  greater  the  amount  of  acid  the  more 
shaking  is  required  to  give  a  good  emulsion,  until  finally  when 
all  the  oil  has  been  changed  into  fatty  acid  and  glycerine  we  get 
no  emulsion  at  all,  but  only  a  cloudiness  due  to  the  insoluble  soap 
formed.  In  this  method  we  have  a  simple  means  of  approximately 
estimating  the  increase  of  fatty  acid  in  an  oil  and  of  determining 
when  all  the  oil  has  been  changed  to  acid  and  glycerine.  This 
method  is  not  used  to  determine  the  exact  quantity  of  acid  which 
an  oil  contains,  but  is  used  rather  to  make  a  comparative  estimate 
of  the  amount  of  acid  in  the  same  oil  at  different  times  and  in 
different  oils  at  the  same  time. 

This  method  is  applied  to  the  study  of  the  fat-splitting  pro- 
perties of  pancreatic  juice  in  the  following  manner.  Arrange  a 
series  of  watch-glasses  containing  a  \  per  cent,  solution  of  carbo- 
nate of  sodium.  Take  a  small  test-tube  of  2  c.c.  capacity  and 
place  in  it  \  c.c.  of  pancreatic  juice  and  twice  as  much  neutral 
olive  oil.  Shake  the  tube  and  allow  the  juice  and  oil  to  separate, 
then  pipette  a  drop  of  oil  from  the  surface  and  place  it  on  the 
soda  solution  in  watch-glass  i.  Again,  shake  the  tube  and  allow 
the  oil  and  juice  to  separate,  then  pipette  as  before,  placiftg  a 
drop  of  oil  in  watch-glass  2.  Again  shake  and  pipette  as  before, 
and  repeat  this  process  every  three  or  four  minutes  until  the 
experiment  is  completed.  The  beginning  of  the  experiment  and 
the  time  of  each  pipetting  must  be  carefully  noted.  If  the 
pipettings  are  three  minutes  apart,  then  the  first  drops  of  oil  will 
have  been  exposed  three  minutes  to  the  action  of  pancreatic  juice, 
the  second  drop  six  minutes,  the  third  drop  nine  minutes,  and  so 
on.  By  the  amount  of  spontaneous  emulsion  occurring  in  these 
drops  when  placed  on  the  soda  solution  one  can  comparatively 
estimate  the  quantity  of  fatty  acid  they  contain.  For  example,  in 
an  experiment  such  as  I  have  just  narrated  one  may  find  very  little 
emulsion  in  glass  i,  more  in  2,  a  fair  emulsion  in  3,  good  in  4,  and 
the  maximum   in    5,  and   then   the  emulsion  gradually  decreases. 


i8  PANCREATIC    DIGESTION. 

By  such  experiments  as  this  the  fat-splitting  properties  of  pan- 
creatic juice  can  be  beautifully  demonstrated,  and  an  idea  formed 
of  the  rapidity  of  its  action.  There  is  a  possible  element  of  error 
in  this  method  which  had  better  be  spoken  of  here.  It  would 
seem  that  the  alkali  of  the  pancreatic  juice  w^ould  combine  with 
the  fatty  acids,  forming  soap,  and  in  this  way  the  oil  would  soon 
be  emulsified  in  the  juice  itself  and  not  separate  after  shaking. 
This  would  indeed  be  a  serious  drawback  if  it  actually  occurred, 
but  in  truth  it  does  not  occur  until  late  in  the  experiment,  after 
we  have  obtained  the  information  we  sought  by  the  spontaneous 
emulsion  method.  It  is  true  that  after  a  large  quantity  of  acid 
has  developed  and  by  repeated  shaking  we  get  an  emulsion  of 
oil  in  the  juice  which  somewhat  interferes  with  the  method. 
Although  the  sodium  in  the  pancreatic  juice  exists  in  the  form 
of  a  carbonate,  it  seems  to  be  peculiarly  associated  w^ith  some 
other  substance  which  interferes  with  its  combining  with  fatty 
acid  in  the  formation  of  soaps.  This  may  be  illustrated  by  the 
following  interesting  experiment.  Place  in  a  small  test-tube 
drawn  out  like  a  pipette  equal  quantities  of  pancreatic  juice  and 
neutral  olive  oil,  ^  c.c.  each.  Shake  the  tube  and  set  aside  for 
twenty-four  hours.  At  the  expiration  of  this  time  break  the 
pipette  point  and  allow  the  contents  of  the  tube  to  escape  slowly 
through  the  opening  thus  formed  in  the  bottom  of  the  tube. 
The  pancreatic  juice,  being  at  the  bottom,  is  the  first  to  escape, 
and  it  is  clear  and  strongly  alkaline  ;  then  comes  the  oil  which 
formed  the  upper  layer,  and  it  is  strongly  acid.  Here  we  have 
a  rancid  oil  and  an  alkaline  fluid  in  contact  for  twenty-four  hours 
with  very  little  soap  formation.  This  experiment  clearly  indi- 
cates that  something  interferes  with  the  formation  of  soap  from 
the  alkalies  of  the  pancreatic  juice.  This  is  a  plausible  expla- 
nation of  why  the  element  of  error  caused  by  soap  formation 
does  not  interfere  with  the  practical  application  of  the  method. 
But  even  the  small  element  of  error  which  is  introduced  by  soap 
formation  may  be  reduced  to  a  minimum  by  using  small  quan- 
tities of  juice  and  three  or  four  times  as  much  oil,  and  in  that 
way  the  quantity  of  soda  is  greatly  reduced  and  the  action  of 
the  juice  is  but  slightly  retarded.  This  latter  seems  a  strange 
statement,  yet  I  have  found  in  my  experiments  that  within  the 
limits  named,  the  same  quantity  of  juice  splits  large  quantities 
of  oil   almost  as  readily  as  small.      In   passing,  let  me  again  call 


B.  K.  RACHFORD.  19 

attention  to  the  experiment  above  narrated  as  a  simple  and  strik- 
ing lecture  experiment.  The  alkalinity  of  the  juice  and  the 
acidity  of  the  oil  as  it  follows  through  the  same  opening  may  be 
demonstrated  by  litmus  paper  or  solution.  With  these  details  as 
to  method  we  are  prepared  to  consider  pancreatic  juice  and  its 
action  on  neutral  fats. 

1.  The  pancreatic  juice  of  the  rabbit  is  alkaline  and  remains 
so  for  some  time  after  it  is  removed.  On  two  occasions  I  tested 
juice  that  had  stood  exposed  at  room  temperature  for  twenty- 
four  hours  and  found  it  alkaline  and  physiologically  active.  Dif- 
ferent specimens  of  pancreatic  juice  may  vary  in  physiological 
activity.  As  a  rule,  the  juice  obtained  from  a  fistula  that  has 
been  acting  several  hours  is  not  as  active  as  juice  from  the  same 
fistula  obtained  soon  after  the  operation. 

2.  If  pancreatic  juice  be  shaken  with  neutral  olive  oil,  the 
oil  rapidly  takes  on  an  acid  reaction.  That  this  acidity  is  due  to 
fatty  acid  is  shown  by  the  facts  that  all  the  acid  may  be  extracted 
with  ether  and  the  oil  made  emulsible  by  its  presence.  The 
gradual  yet  rapid  development  of  fatty  acid  by  the  action  of 
pancreatic  juice  on  neutral  olive  oil  may  be  beautifully  demon- 
strated by  pipetting  drops  of  oil  at  intervals  from  the  surface  of 
a  mixture  of  pancreatic  juice  and  neutral  olive  oil  and  placing 
them  on  a  \  per  cent,  solution  of  carbonate  of  sodium  in  a  series 
of  watch-glasses.  Soon  we  have  a  slight  emulsion,  then  more 
and  more  until  the  maximum  is  reached,  then  the  amount  of 
emulsion  becomes  less  and  less  as  too  much  fatty  acid  is  devel- 
oped, until  finally  we  have  no  spontaneous  emulsion  at  all.  That 
an  excess  of  fatty  acid  is  the  cause  of  the  decrease  and  cessation 
of  spontaneous  emulsion  may  be  demonstrated  as  follows.  Take 
a  drop  of  oil  from  a  mixture  of  oil  and  pancreatic  juice  after  it 
has  passed  the  limits  of  spontaneous  emulsibility  and  mix  it  with 
neutral  olive  oil,  and  the  mixture  is  spontaneously  emulsible.  In 
one  experiment,  for  example,  I  took  one  drop  of  oil  that  had 
passed  the  stage  of  spontaneous  emulsibility  and  mixed  it  with 
four  drops  of  neutral  olive  oil,  and  one  drop  of  the  mixture  on 
soda  solution  gave  a  beautiful  spontaneous  emulsion.  Here  one 
drop  of  the  oil  acted  on  by  the  juice  contained  sufficient  fatty 
acid  to  make  five  drops  of  oil  spontaneously  emulsible,  that  is, 
to  give  five  drops  of  oil  about  5^  per  cent,  of  fatty  acid.  The 
drop  of  oil  acted  on  by  the  juice  must  therefore  have  contained 


20  PANCREATIC    DIGESTION. 

about  30  per  cent,  of  fatty  acid  and  the  time  required  to  develop 
it  was  thirty-five  minutes.  Since  30  percent,  of  acid  is  so  quickly 
developed,  it  seems  a  fair  inference  that  the  prolonged  action  of 
the  juice  would  change  all  the  oil  into  fatty  acid  and  glycerine, 
and  such,  in  fact,  is  found  to  be  the  case. 

3.  All  the  oil  is  split  into  fatty  acid  and  glycerine  by  from 
one  to  two  hours'  action  of  the  pancreatic  juice — time  varies 
with  the  specimen  of  the  juice.  This  may  be  shown  by  pipetting 
such  fatty  matter  from  the  surface  of  the  juice  and  shaking  it 
with  soda  solution  and  no  emulsion  will  result,  simply  a  little 
clouding,  such  as  occurs  when  fatty  acid  is  shaken  with  soda 
solution.  But  if  one  drop  of  this  same  fatty  matter  be  mixed 
with  six  or  eight  drops  of  neutral  olive  oil,  this  mixture  will,  on 
being  shaken  with  soda  solution,  give  a  good  emulsion.  This 
experiment  is  best  performed  by  adding  a  small  quantity  of  bile 
to  the  juice  before  adding  the  oil.  The  bile  does  not  interfere 
with  the  fat-splitting  action  of  the  juice,  but  it  does  interfere 
with  the  formation  of  an  emulsion,  and  for  that  reason  the  oil 
and  juice  continue  to  separate  after  shaking. 

4.  The  time  required  for  pancreatic  juice,  acting  in  glass 
tubes  at  room  temperature,  to  develop  sufficient  fatty  acid  (5^ 
per  cent.)  in  neutral  olive  oil  to  give  the  maximum  spontaneous 
emulsion  varies  with  different  specimens  of  the  juice  and  with 
the  amount  of  shaking  to  which  the  juice  and  oil  are  subjected, 
but  the  average  time  as  taken  from  my  experiments  was  twenty 
minutes.  In  very  active  specimens  of  the  juice  it  occurred  as 
early  as  seven  minutes,  and  in  very  poor  specimens  as  late  as 
sixty  minutes.  I  also  found  that  the  juice  did  not  act  more 
rapidly  in  a  basin  of  intestine  than  in  the  test-tubes.  In  these 
experiments  the  resected  intestine  containing  the  pancreatic 
papilla  was  held  by  a  fenestrated  quadrilateral  clamp  made  for 
the  purpose,  and  into  the  basin  of  the  intestine  thus  formed  the 
pancreatic  juice  would  ooze.  Neutral  olive  oil  was  dropped  into 
this  basin  and  mixed  with  the  pancreatic  juice,  and  this  oil  did 
not  become  spontaneously  emulsible  more  quickly  than  the  oil 
in  the  test-tubes,  but  the  conditions  here  are  also  far  from  resem- 
bling those  occurring  in  the  normal  duodenum,  and  the  average 
rate  of  fat-splitting  as  established  by  these  experiments  is  probably 
considerably  below  the  rate  at  which  fats  are  split  in  the 
duodenum.     It   is  probable  that  the  time  required  by  the  most 


B.  K.  RACHFORD.  21 

active  juice  more  nearly  represents  the  rapidity  of  action  of  pan- 
creatic juice  in  the  duodenum. 

5.  The  action  of  the  pancreatic  juice  on  most  of  the  fats  is 
rapid  and  complete. 

Castor  oil  is  a  notable  exception  to  this  rule,  as  only  a  very 
small  quantity  of  acid  is  developed  in  it  by  the  action  of  pancreatic 
juice  for  five  hours  at  37°  C.  Castor  oil  is  therefore  practically 
indigestible,  and  this  may  in  part  account  for  its  cathartic  action. 

Pancreatic  juice  acts  slowly  on  fats  which  have  a  melting 
point  above  body  temperature,  but  it  is  an  interesting  physiologi- 
cal fact  that  their  solidity  at  body  temperature  does  not  prevent 
their  being  split.  vSpermaceti,  for  example,  the  melting  point 
of  which  is  above  38°  C,  is  slowly  split  by  the  action  of  the  pan- 
creatic juice. 

6.  As  I  have  previously  said,  the  pancreatic  juice  of  the 
rabbit  and  neutral  olive  oil  when  shaken  together  show  very 
slight  tendency  to  the  formation  of  an  emulsion,  and  it  is  only 
after  considerable  acid  has  developed  that  repeated  shaking 
will  give  a  mixture  resembling  an  imperfect  emulsion.  But  if 
we  mix  and  shake  at  intervals  one  part  of  neutral  olive  oil  and 
one  part  of  pancreatic  juice  for  about  fifteen  minutes,  and  then 
add  six  parts  of  soda  solution,  we  get  at  once  an  apparently 
good  emulsion.  This  emulsion  does  not  remain  good;  it  always 
in  the  course  of  an  hour  or  two  clears  by  creaming,  %vhen  the 
whole  mixture  will  be  found  to  have  a  strong  acid  reaction  due  to 
the  large  quantity  of  fatty  acid  developed.  Whatever  may  be 
the  explanation  of  the  clearing  of  this  pancreatic  emulsion,  the 
fact  remains  that  an  emulsion  will  form  in  the  presence  of  pan- 
creatic juice  if  carbonate  of  sodium  solution  be  added,  but  it 
does  not  remain  permanent. 

7.  A  permanent  pancreatic  emulsion  may  be  formed  by 
pipetting  the  oil  from  the  surface  of  a  tube  containing  oil  and 
juice  and  shaking  it  with  the  carbonate  of  sodiuni  solution.  The 
emulsion  formed  in  this  way  remains  very  much  the  same  for  an 
indefinite  length  of  time.  In  this  experiment  the  oil  is  made 
emulsible  by  the  action  of  the  juice  and  is  then  separated  from 
it  and  emulsified  with  the  soda  solution  ;  the  emulsion  itself  con- 
tains no  pancreatic  juice  and  therefore  does  not  clear.  This 
permanent  pancreatic  emulsion  reacts  to  emulsion  -  destroying 
agents  and  soap  dissolvers  very  like  a  fatty  acid  emulsion  made 


22  PANCREATIC    DIGESTION. 

with  rancid  oil  and  sodium  solution.  For  example,  it  is  not 
destroyed  by  the  addition  of  bile  or  fatty  acids,  but  is  destroyed 
by  mineral  acids,  resisting  hydrochloric  better  than  nitric  and 
sulphuric  acids.  The  pancreatic  emulsion  also  resembles  the 
simple  rancid  oil  emulsion  in  that  an  appreciable  length  of  time 
must  elapse  after  its  formation  before  it  reaches  its  greatest 
degree  of  stability.  This  may  be  demonstrated  by  adding  bile 
in  excess  immediately  after  the  formation  of  the  emulsion,  when 
it  destroys  the  emulsion  by  creaming,  but  if  the  bile  be  added 
later  no  such  effect  is  produced.  It  also  resembles  the  rancid  oil 
emulsion  in  that  it  cannot  form  at  all  in  the  presence  of  bile. 

The  most  important  application  of  the  method  I  have  described 
is  in  obtaining  comparative  information  concerning  the  fat-split- 
ting properties  of  pancreatic  juice.  This  application  of  the 
method  may  best  be  explained  by  detailing  an  experiment  in- 
quiring into  the  difference  in  the  rapidity  of  action  of  pan- 
creatic juice  at  room  (i8°  C.)  and  at  body  temperature  (37°  C). 

Arrange  two  rows  of  w^atch-glasses  containing  a  \  per  cent. 
carbonate  of  sodium  solution.  Take  two  small  test-tubes,  ^  c.c. 
of  the  same  pancreatic- juice  in  each,  and  to  each  tube  add  ^  c.c. 
of  neutral  olive  oil.  Shake  both  tubes  equally  and  place  one  of 
them  (A)  in  a  sand  bath  kept  in  an  oven  at  37°  C.  and  leave  the 
other  (B)  at  room  temperature.  At  the  expiration  of  three 
minutes  pipette  a  drop  of  oil  from  A  and  place  it  in  watch- 
glass  I,  row  I  ;  then  as  quickly  as  possible,  with  a  clean  pipette, 
take  a  drop  from  B  and  place  it  in  watch-glass  i,  row  2.  Both 
tubes  are  shaken  and  replaced  and  at  the  expiration  of  three 
minutes  a  drop  is  again  pipetted  from  the  surface  of  each.  That 
from  A  is  placed  in  row  i,  that  from  B  in  row  2.  This  process 
is  repeated  again  and  again  to  the  end  of  the  experiment.  At 
the  close  of  the  experiment  if  will  be  found  that  the  emulsion 
occurs  almost  twice  as  quickly  in  row  i  as  in  row  2.  The  three- 
minute  drop  of  oil  from  A  gives  as  good  an  emulsion  as  the 
six-minute  drop  of  oil  from  B,  and  the  nine-minute  drop  of  oil 
from  A  gives  the  same  emulsion  as  the  eighteen-minute  drop  of 
oil  from  B.  Since  these  tubes  were,  apart  from  the  temperature, 
treated  as  nearly  alike  as  possible,  we  infer  that  pancreatic  juice 
acts  about  twice  as  rapidly  at  37°  C.  as  it  does  at  18°  C.  The 
average  ratio  of  increased  rapidity  of  action,  taken  from  my 
experiments,  was  as  one  to  one  and  eight-tenths. 


B.   K.  RACHFORD.  23 

Whatever  objections  may  be  urged  against  the  absolute  accu- 
racy of  the  figures  obtained  by  this  method,  the  same  do  not 
apply  to  the  comparative  accuracy  of  these  figures.  Even  though 
we  may  not  be  able  by  this  method  to  estimate  the  amount  of 
acid  produced  by  pancreatic  juice  in  nine  minutes  acting  at  37°  C, 
we  do  know  by  this  method,  whatever  this  amount  may  be,  that 
it  requires  one  and  eight-tenths  times  as  long  for  pancreatic  juice 
to  produce  the  same  amount  at  18*^  C.  In  comparative  experi- 
ments such  as  this  it  is  not  necessary  nor  practicable  to  have  an 
equal  length  of  time  between  the  pipettings,  but  it  is  important 
that  the  tubes  should  be  shaken  at  as  nearly  the  same  time  and 
pipetted  at  as  nearly  the  same  time  as  possible,  so  that  the  oil 
drops  to  be  compared  by  spontaneous  emulsibility  may  have  been 
exposed  to  the  action  of  the  juice  for  the  same  length  of  time, 
thus  establishing  the  comparative  accuracy  of  the  results. 

The  great  value  and  wide  application  of  this  method  is  seen 
in  the  study  of  the  influence  of  bile  and  other  agents  on  the 
fat-splitting  action  of  pancreatic  juice. 

Bile  alone  does  not  split  fats.  This  seems  a  well-established 
physiological  fact,  which  may  be  confirmed  by  shaking  neutral 
olive  oil  and  bile  in  a  test-tube  and  pipetting  the  oil  at  intervals 
to  the  surface  of  a  carbonate  of  sodium  solution  as  in  previous 
pancreatic  experiments,  when  it  will  be  found  that  oil  shaken 
with  bile  for  twenty-four  hours  does  not  become  emulsible.  The 
value  of  this  method  is  here  most  conspicuous,  as  the  emulsibility 
of  the  oil  could  not  be  tested  in  the  presence  of  the  bile,  because 
the  bile  would  prevent  an  emulsion  even  if  the  fatty  acid  had 
been  developed.  But  in  this  method  the  oil  is  separated  from 
the  bile  after  they  have  been  in  contact  twenty-four  hours  and  its 
emulsibility  tested,  and  in  this  point  lies  the  great  value  and 
wide  application  of  the  method,  since  the  very  agents,  such  as 
bile  and  hydrochloric  acid,  which  have  the  greatest  influence  on 
the  fat-splitting  action  of  pancreatic  juice  are  the  agents  which 
interfere  with  the  formation  of  emulsions. 

Fresh  rabbit  bile  removed  from  the  gall-bladder  was  used  in 
all  my  experiments. 

In  every  comparative  experiment  the  pancreatic  juice  which 
had  been  collected  in  a  single  tube  was  divided  into  two,  three 
or  four  equal  parts,  according  to  the  number  of  tubes  used  in  the 
experiment.     The  bile  was  also  shaken  and  divided  just  previous 


24  PANCREATIC    DIGESTION. 

to  the  experiment.  In  this  way  I  could  be  reasonably  sure  that 
I  was  working  with  the  same  bile  and  same  pancreatic  juice  in 
all  the  tubes. 

By  the  methods  described  I  reached  the  following  conclusions  : 

1.  An  equal  amount  of  fresh  rabbit's  bile  will,  on  being 
added  to  rabbit's  pancreatic  juice,  greatly  hasten  its  fat-splitting 
action  in  the  ratio  of  three  and  one-fifth  to  one.  In  experiments 
of  this  kind,  tube  A  contains  \  c.c.  of  pancreatic  juice  and  \  cc. 
of  neutral  olive  oil,  and  tube  B  contains  \  c.c.  pancreatic  juice 
and  \  c.c.  bile  and  f  c.c.  of  neutral  olive  oil.  These  tubes  are 
treated  alike  and  the  emulsibility  of  the  oil  is  tested  from  time 
to  time  as  previously  described.  In  this  way  the  comparative 
rapidity  with  which  fatty  acid  is  developed  in  the  oils  may  be 
determined.  It  is  evident  that  in  ever}^  experiment  we  can  have 
two  sets  of  figures  from  which  to  make  our  average,  viz.,  the 
time  required  for  the  beginning  and  the  time  required  for  the 
maximum  of  spontaneous  emulsion.  In  my  general  averages  I 
have  used  both  sets  of  figures,  striking  an  average  between  them, 

2.  An  equal  quantity  of  a  ^  per  cent,  solution  of  hydrochloric 
acid  will,  on  being  added  to  pancreatic  juice,  retard  its  fat-split- 
ting action  in  the  ratio  of  two-thirds  to  one. 

^.  A  mixture  of  equal  quantities  of  bile  and  a  \  per  cent, 
hydrochloric  acid  solution  will,  on  being  added  to  pancreatic 
juice,  greatly  hasten  its  fat-splitting  action  in  the  ratio  of  four  to 
one.  The  bile  not  only  neutralizes  the  retarding  influence  of  the 
hydrochloric  acid  on  the  fat-splitting  properties  of  the  juice,  but 
it  really  acts  more  powerfully  in  hastening  the  action  of  the  juice 
when  in  the  presence  of  this  acid  than  it  does  when  acting  alone. 
The  contents  of  a  series  of  tubes  will  best  explain  the  class  of  ex- 
periments upon  which  this  statement  is  based. 

Tube  A  contains  \  c.c.  pancreatic  juice  and  |  c.c.  neutral 
olive  oil.  Tube  B  contains  ^  c.c.  of  pancreatic  juice,  \  c.c.  of 
bile  and  |  c.c.  neutral  olive  oil.  Tube  C  contains  \  c.c.  of  pan- 
creatic juice,  Ye  c.c.  of  bile.  Ye  c.c.  of  a  \  per  cent,  hydrochloric 
acid  solution,  and  f  c.c.  of  neutral  olive  oil. 

Three  rows  of  watch-glasses  containing  soda  solution  having 
been  arranged  for  the  reception  of  the  oil  drops,  the  tubes  are 
now  shaken  and  pipetted  as  in  previous  experiments  and  the 
time  and  the  result  are  carefully  noted.  In  row  i  containing  the 
oil    drop    from    A,   the   emulsion   begins    in   eight   minutes,   and 


B.   K.   RACHFORD.  25 

reaches  the  maximum  in  twenty  minutes.  In  row  2  containing 
the  oil  from  B,  the  emulsion  begins  in  two  and  a  half  minutes 
and  reaches  the  maximum  in  six  and  a  quarter  minutes.  In  row  3 
containing  the  oil  drop  from  C,  the  emulsion  begins  in  two 
minutes  and  reaches  the  maximum  in  five  minutes.  These  figures 
are  the  averages  of  a  number  of  experiments. 

4.  If  an  equal  quantity  of  a  3  per  cent,  solution  of  glycocho- 
late  of  soda  be  mixed  with  pancreatic  juice  it  hastens  the  fat- 
splitting  action  of  the  juice  in  the  ratio  of  two  and  one-fifth  to 
one. 

5.  A  mixture  of  equal  quantities  of  a  3  per  cent,  solution  of 
glycocholate  of  soda  and  a  \  per  cent,  solution  of  hydrochloric 
acid  will,  on  being  added  iu  equal  quantities  to  pancreatic  juice, 
hasten  its  fat-splitting  action  in  the  ratio  of  two  and  one-third 
to  one. 

The  glycocholate  of  soda  solution,  like  the  bile,  not  only  neu- 
tralized the  retarding  influence  of  hydrochloric  acid  on  the  fat- 
splitting  action  of  the  juice,  but  it  really  acts  more  powerfully  in 
hastening  the  action  of  the  juice  when  in  the  presence  of  the  acid 
than  it  does  Avhen  acting  alone.  It  must  also  be  noted  that  the 
glycocholate  of  soda  does  not  act  as  powerfully  in  hastening  the 
fat-splitting  action  of  the  juice  as  the  bile  does.  In  the  presence 
of  bile  the  juice  acts  three  and  one-fifth  times  as  rapidly  as  it 
does  alone,  and  in  the  presence  of  a  3  per  cent,  solution  of  glyco- 
cholate of  soda  it  acts  two  and  a  fifth  times  as  rapidly.  In 
the  presence  of  bile  and  hydrochloric  acid  it  acts  four  times  as 
rapidly,  and  in  the  presence  of  glycocholate  of  soda  and  hydro- 
chloric acid  it  acts  two  and  four-fifths  as  rapidly.  From  this  I 
infer  that  this  property  of  the  bile  is  chiefly  but  not  wholly  due 
to  the  glycocholate  of  soda  it  contains.  The  class  of  experiments 
by  which  these  conclusions  were  reached  is  illustrated  in  Plate  I,' 
which  is  in  part  reproduced  from  a  photograph. 

6.  If  one  part  of  pancreatic  juice  be  diluted  with  five  parts  of 
a  \  percent,  carbonate  of  sodium  solution  its  fat-splitting  proper- 
ties will  be  greatly  retarded — in  the  ratio  of  one  to  eight — and 
further  dilution  with  soda  solution  gives  greater  retardation-,  this 
property  of  the  juice  being  practically  destroyed  when  it  is  ten 
times  diluted  v,'ith  this  strength  of  soda  solution.  That  this  re- 
tarding influence   is   due  to  the  soda,  and   not   to  the  dilution,  is 

I   See  original  paper. 


26  PANCREATIC    DIGESTION. 

shown  by  the  fact  that  if  pancreatic  juice  be  dihited  with  five 
parts  of  distilled  water,  its  fat-splitting  action  is  very  slightly,  if 
at  all,  retarded. 

The  retarding  influence  of  soda  solution  may  be  shown  by  the 
same  kind  of  experiments  used  to  show  the  influence  of  bile, 
hydrochloric  acid.  etc..  on  the  fat-splitting  properties  of  pan- 
creatic juice.  But  it  seems  possible  that  there  might  be  consider- 
able cause  of  error  in  this  class  of  experiments,  because  of  the 
presence  of  soda  solution  in  one  of  the  tubes.  In  an  experiment 
of  this  kind,  for  example,  one  tube  contains  \  c.c.  of  pancreatic 
juice  and  f  c.c.  of  neutral  olive  oil,  the  other  contains  in  addition 
to  the  same  quantity  of  juice  and  oil  ^  1%  c.c.  of  soda  solution. 
In  pipetting  oil  from  the  surface  of  two  such  tubes  to  test  its 
spontaneous  emulsibility,  will  not  the  result  be  greatly  vitiated 
by  the  soda  solution  in  one  of  the  tubes,  neutralizing  the  fatt\- 
acid  as  soon  as  formed.-  Theoretically  this  would  seem  to  be  an 
important  source  of  error,  but  practically  it  is  not  of  very  great 
importance,  since  the  results  obtained  by  this  method  correspond 
closely  to  those  obtained  by  another  method  which  has  not  this 
source  of  error.  The  following  experiment  will  illustrate  this 
method.  Take  two  small  glass  tubes.  In  one  place  \  c.c.  of 
pancreatic  juice  and  \  c.c.  of  neutral  olive  oil.  Shake  four  or 
five  minutes  and  add  'Ys  c.c.  of  soda  solution  and  an  immediate 
emulsion  will  result.  To  the  other  tube  add -^  c.c.  pancreatic  juice 
and  \  c.c.  neutral  olive  oil  and  "^3  c.c.  of  soda  solution.  Shake, 
and  the  emulsion  will  not  appear  for  thirty  or  thirty-five  minutes. 
In  the  first  tube,  the  pancreatic  juice  acting  alone  on  the  neutral 
oil  produced  enough  acid  in  four  or  five  minutes  to  make  the  oil 
emulsible  on  shaking  it  with  the  soda  solution.  But  in  the  tube 
2,  the  presence  of  the  soda  solution  retarded  the  action  of  the 
juice  so  that  it  required  thirty  minutes  to  produce  sutHcient  fatty 
acid  to  give  an  emulsion.  Carbonate  of  soda  solution  therefore 
retards  the  fat-splitting  action  of  pancreatic  juice  in  the  ratio 
above  given. 

In  the  accompanying  diagram  I  have  taken  a  line  twenty 
millimetres  long  to  represent  the  working  power  of  pancreatic 
juice  acting  alone  at  room  temperature.  The  other  lines  repre- 
sent the  comparative  working  power  of  pancreatic  juice  under 
the  conditions  named,  and  were  obtained  from  averaging  all  my 
experiments. 


B.  K.  RACHFORD.  27 

DIAGRAM    SHOWING    THE    INFLUENCE    OF    BILE    AND    OTHER 

AGENTS    ON    THE    FAT-SPLITTING    PROPERTIES 

OF    PANCREATIC    JUICE. 

Pancreatic  juice  at  18°  C. 

20  Mil.     — ^^^^— ^—     I 

Pancreatic  juice  at  37°  C. 

36  Mil.     — ^-^^^^^—     I 


Pancreatic  juice  at  iS°  C.  and  HCl. 
13  Mil.     "— 


Pancreatic  juice  at  18°  C.  and  glycocholate  of  soda. 

44  Mil. i^ 

Pancreatic  juice  at  18°  C.  and  glycocholate  of  soda  and  HCl. 
56  Mil.  '  li 

Pancreatic  juice  at  18°  C.  and  bile. 

64  Mil.     ~^ __^^^_     If 

Pancreatic  juice  at  iS°  C.  and  bile  and  HCl. 
80  Mil.  '  4 

The  above  diagram  and  accompanying  figures  are  offered  as 
the  clearest  and  briefest  manner  of  expressing  the  difference  in 
the  rapidity  of  action  of  the  various  mixtures.  It  is  not  even 
hoped  that  these  figures  are  absohitely  correct,  but  it  is  my  belief 
that  relatively  they  are  approximately  correct,  and  therefore  have 
an  all-important  bearing  on  the  pancreatic  digestion  of  fats.  We 
may  sinnmarize  : 

1.  Pancreatic  juice  can,  acting  alone,  do  a  certain  piece  of 
work  in  x  minutes,  viz.,  develop  in  neutral  olive  oil  a  sufficient 
quantity  of  fatty  acid  to  give  the  best  spontaneous  emulsion. 

2.  Pancreatic  juice  acting  in  the  presence  of  five  parts  of  a 
\  per  cent,  carbonate  of  soda  solution  will  require  "^x  minutes  to 
do  the  same  work,  and  in  the  presence  of  ten  parts  of  the  same 
solution  its  action  will  be  almost  destroyed. 

3.  Pancreatic  juice  acting  in  the  presence  of  an  equal  quan- 
tity of  a  \  per  cent,  solution  of  hydrochloric  acid  will  require 
Y2-V  minutes  to  do  the  same  work. 

4.  Pancreatic  juice  acting  in  the  presence  of  an  equal  quan- 
tity of  a  mixture  of  bile  and  a  \  per  cent,  hydrochloric  acid  solu- 
tion will  require  only  \x  minutes  to  do  the  same  work. 

From  the  last  two  propositions  it  would  follow  that,  if  bile 
be  added  to  pancreatic  juice  which  is  acting  in  the  presence  of 


28  PANCREATIC    DIGESTION. 

hydrochloric  acid,  the  fat-splitting  action  of  the  juice  will  be 
hastened  as  '■'' ji  to  \  or  as  six  to  one,  and  reversely,  that  if  the 
bile  be  withdrawn  or  cut  off  from  pancreatic  juice  which  has 
previously  been  acting  in  the  presence  of  both  bile  and  hydro- 
chloric acid,  the  fat-splitting  properties  of  the  juice  will  be 
retarded  as  six  to  one. 

APPLICATION    OF    THESE    PRINCIPLES    TO    THE     INTESTINAL 
DIGESTION    OF    FATS. 

It  is  needless  to  say  that  my  experiments  were  planned  with 
the  idea  of  placing  pancreatic  juice  under  conditions  as  nearly 
as  possible  resembling  those  under  which  it  acts  in  the  intestine. 
The  influence  of  a  \  percent,  solution  of  HCl  was  studied  because 
of  the  presence  of  this  acid  in  the  duodenum,  where  the  pancreatic 
juice  comes  in  contact  with  the  fats.  The  influence  of  bile 
and  of  a  mixture  of  bile  and  hydrochloric  acid  were  studied 
for  the  same  reason.  The  influence  of  dilution  with  a  \  per 
cent,  solution  of  carbonate  of  sodium  was  studied  because  it 
was  thought,  that,  as  the  pancreatic  juice  passed  downward 
into  the  small  intestine,  it  might  be  subjected  to  some  such 
influence,  since  the  succus  entericus  contained  this  percent- 
age of  carbonate  of  soda.  The  conclusions  therefore  to  which 
I  have  arrived  must,  if  true,  have  a  very  important  bearing 
in  the  explanation  of  the  intestinal  digestion  of  fats.  I  infer 
from  my  experiments  that  in  the  duodenum  the  mixture  of  bile 
and  hydrochloric  acid  furnishes  the  best  known  conditions  for 
expediting  the  fat-splitting  action  of  pancreatic  juice,  and  the 
cutting  off  of  the  bile  would  retard  the  fat-splitting  action  of  the 
juice  six  times.  It  may  also  be  of  some  physiological  importance 
to  note  that  the  agents  bile  and  HCl  which  expedite  the  fat-split- 
ting absolutely  preclude  the  formation  of  emulsions.  The  duo- 
denum therefore  offers  the  most  favorable  conditions  for  the 
splitting  of  the  fats  and  the  most  unfavorable  for  their  emulsifi- 
cation.  In  the  jejunum  and  ileum  these  conditions  seem  to  be 
exactly  reversed.  The  intestinal  juice  containing,  as  it  does,  \ 
per  cent,  of  carbonate  of  soda,  would  not  only  furnish  the  con- 
ditions for  the  spontaneous  emulsification  of  the  rancid  fats,  but 
would  also  retard  the  fat-splitting  action  of  the  pancreatic  juice. 
I  do  not  wish  to  express  the  belief  that  intestinal  juice  plays  just 
such   a  role  as  this   in  the   intestinal   digestions  of  fats,  but  only 


B.  K.  RACHFORD.  29 

offer  it  as  a  deduction  from  test  -  tube  experiments,  thinking  it 
may  have  some  physiological  bearing. 

From  my  experiments  I  infer  that  pancreatic  juice  must  act 
very  rapidly  under  the  favorable  conditions  found  in  the  duode- 
num. In  some  of  my  experiments  at  room  temperature,  good 
specimens  of  pancreatic  juice,  aided  by  the  presence  of  bile  and 
hydrochloric  acid,  produced,  in  neutral  olive  oil,  ^\  per  cent,  of 
fatty  acid  in  two  minutes.  At  body  temperature  this  work  would 
have  been  accomplished  in  one  minute,  and  under  the  favorable 
conditions  offered  by  the  duodenum  it  would  probably  have  been 
done  in  even  less  time. 

This  rapidity  of  action  of  pancreatic  juice  is  of  great  physio- 
logical importance,  since  it  is  evident  that  at  this  rate  all  the  fats 
would  be  split  into  fatty  acid  and  glycerine  in  the  time  required 
for  intestinal  digestion,  unless  this  action  of  the  juice  was  checked 
or  retarded  in  some  manner. 

IMPORTANCE    OF    BILE    IN    THE    INTESTINAL    DIGESTION 
OF    FATS. 

The  various  conditions  which  have  an  influence  on  the  intes- 
tinal digestion  of  fats  have  been  developed  by  natural  selection, 
and  so  far  as  we  know  they  are  the  best  for  the  purposes  they 
serve.  The  comparative  immobility  of  the  duodenum,  its  close 
attachment  to  the  head  of  the  pancreas,  its  horse-shoe  shape,  all, 
no  doubt,  have  an  influence  on  the  rate  of  passage  of  food-stuffs. 
This  rate,  which  is  chiefly  controlled  by  these  and  other  ana- 
tomical conditions,  was  established  to  accord  with  normal  diges- 
tive functions,  and  by  this  mechanism  the  fats  are  exposed  to  the 
action  of  pancreatic  juice  just  long  enough  to  allow  for  whatever 
action  that  juice  may  have  in  fat  digestion.  Let  us  suppose  that 
under  normal  conditions  the  fats  are  exposed  in  the  duodenum 
to  the  action  of  pancreatic  juice  for  .v  minutes,  and  that  this  time 
is  just  sufficient  to  allow  for  whatever  fat-splitting  is  necessary 
at  this  point.  Now,  if  the  bile  be  cut  off,  the  rate  of  passage  of 
the  food-stuffs,  which  is  chiefly  controlled  by  anatomical  condi- 
tions, remaining  the  same,  the  fat  would  still  be  exposed  to  the 
action  of  the  juice  for  only  x  minutes.  But  since  in  the  absence 
of  the  bile  the  pancreatic  juice  is  able  to  accomplish  only  one-sixth 
of  the  fat-splitting  which  it  normally  does,  it  would  follow  that 
the  fats  would  pass  with  only  one-sixth  of  the  amount  of  splitting 


30  PANCREATIC    DIGESTION. 

that  normally  occurs,  and  since  the  splitting  of  the  fat  is,  as  recog- 
nized by  all  physiologists,  a  necessary  preliminary  step  in  fat 
digestion,  it  would  follow  that  the  fats  would  pass  in  great  part 
undigested.  This  gives  to  bile  a  most  important  and  definite 
position  among  the  juices  which  assist  in  fat  digestion,  since  we 
have  here  pointed  out  at  least  one  of  the  ways  in  which  it  exerts 
its  wonderful  influence  in  fat  digestion.  Physiologists  have  been 
led  to  believe,  through  much  clinical  and  experimental^  evidence, 
that  the  bile  was  necessary  to  fat  digestion.  How  and  where 
it  acted  has  been  one  of  the  greatest  of  physiological  mysteries. 
The  experiments  of  Westinghausen'-^  seemed  to  show  that  bile 
promoted  the  passage  of  the  fats  through  membranes,  and  this 
was  thought  by  some  physiologists  to  have  a  bearing  on  the 
absorption  of  fats.  But  since  the  publication  of  Groeper^  deny- 
ing that  bile  had  any  such  action  we  have  been  quite  as  much  at 
sea  as  ever  in  explaining  the  action  of  bile  in  fat  digestion. 

I   wish   to  thank  Professor  Gad  for   his   kindness   and  advice 
during  the  prosecution  of  these  studies. 

1  Of  special  interest  are  the  recent  experiments  of  A.  Dastre  in  the 
Arch,  de  Physiologic  et  Pathologie,  Paris. 

2  Archiv  f.  Anat.  ti.  Phys.,  1873. 

3  Archiv  f.  Anat.  u.  Phys.,  1889. 


Reprinted  from  the  Amerirau  Jotir^ial  of  the  Medical  Sciences^ 
March,  18i>2. 


IL— FAT-DIGESTION. 


During  the  spring  and  summer  of  1S90,  in  the  Berlin  Physio- 
logical Laboratory,  I  made  a  study  of  the  fat-splitting  properties 
of  pancreatic  juice.  I  read  a  paper  on  this  subject  before  the 
physiological  section  of  the  Tenth  International  Medical  Con- 
gress, and  published  a  detailed  account  of  my  work  in  the  Jour- 
nal  of  Phys to logv .  ( « ) ' 

It  is  my  purpose  in  the  present  paper  to  show  what  application 
my  published  experiments  {a)  may  have  in  explaining  fat-diges- 
tion. That  I  may  do  this  intelligently,  it  will  be  necessary  to 
review  our  present  knowledge  of  this  subject. 

C.  Bernard  believed  that  pancreatic  juice  had  a  twofold  action 
on  fats.  In  the  first  place,  he  said  that  when  neutral  oil  and  pan- 
creatic juice  were  shaken  together  an  instantaneous  emulsion  re- 
sulted, and  in  the  second  place,  that  the  prolonged  action  of 
pancreatic  juice  on  neutral  oil  would  develop  fatty  acid.  He  did 
not  in  any  way  associate  these  two  processes,  and  believed  them 
to  be  due  to  entirely  difl'erent  properties  of  the  juice  ;  the  emul- 
sion being  an  instantaneous  process  and  the  fat-splitting  occur- 
ring only  after  considerable  time.  And  these  two  processes  are 
described  as  separate  and  distinct  properties  of  pancreatic  juice 
in  some  of  our  most  recent  text-books.  But  some  of  the  more 
recent  German  books  have,  upon  the  observations  of  Brucke  and 
Gad,  taught  the  relationship  of  these  processes.  From  the  fact 
that  the  addition  of  fatty  acid  to  neutral  oil  makes  the  mixture 
readily  emulsible  in  an  alkaline  liquid,  they  infer  that  the  emul- 
sion of  fats  in  pancreatic  juice,  as  observed  by  Bernard,  is  not 
due  to  an  emulsion  ferment,  but  is  rather  due  to  the  development 
of  fatty  acid  in  the  fat  by  the  action  of  the  pancreatic  juice. 
They  believe,  therefore,  that  the  first  and  only  specific  action  of 

I  Cambridge,  Eng.,  April,  1S91.  The  mark  (a),  which  occurs  fre- 
quently in  the  text,  always  refers  to  my  published  experiments  in  the 
journal  of  Physiology . 


32  PANCREATIC   DIGESTION. 

pancreatic  juice  on  fats  is  the  splitting  of  them  into  fatty  acid 
and  glycerine,  and  that  by  reason  of  this  an  emulsion  results  in 
the  alkaline  pancreatic  juice ;  but  this  opinion  is  a  matter  of 
inference  from  the  work  of  Brucke  and  Gad  rather  than  frdm 
actual  experiment  with  the  juice  itself.  The  special  emulsion 
ferment  of  Bernard,  although  not  disproven,  is  not  believed  in 
by  many  German  physiologists.  But  physiologists  very  gener- 
ally believe  that  the  alkalinity  of  pancreatic  juice  promotes  the 
emulsification  of  the  rancid  fats,  and  this  latter  opinion  I  have  in 
my  published  experiments  (a)  shown  to  be  erroneous.  We  may, 
therefore,  sum  up  our  present  knowledge  of  the  action  of  pan- 
creatic juice  on  fats  in  very  few  words,  viz.  :  it  splits  neutral 
fats  into  fatty  acid  and  glycerine.  We  know  nothing  about  the 
rapidity  nor  the  influence  of  other  agencies  on  this  action. 

Let  us  now^  note  our  present  knowledge  of  the  action  of  bile  in 
fat-digestion.  The  part  that  bile  plays  in  intestinal  digestion 
seems  one  of  the  most  obscure  of  physiological  problems. 

We  know  that  it  has  a  very  decided  influence  in  fat-digestion  ; 
this  is  proven  by  a  large  amount  of  clinical  and  experimental 
testimony.  The  records  of  clinical  medicine  teem  with  cases 
showing  that  in  occlusion  of  the  bile-ducts  the  fats  are  imper- 
fectly digested,  and  experimental  physiology,  by  ligating  the 
bile -ducts  in  animals,  has  amply  confirmed  this  observation. 
A.  Dastre'  found  that  when  the  bile-duct  of  the  dog  was  ligated 
and  the  bile  turned  into  the  intestinal  canal,  midway  between 
the  stomach  and  caecum,  by  making  a  fistula  between  gall-bladder 
and  intestine  at  this  point,  the  chyle-vessels  remained  transparent 
throughout  that  part  of  the  intestine  between  the  stomach  and 
the  entrance  of  the  bile,  and  only  became  milky  15  cm.  below 
the  point  where  the  bile  was  turned  in. 

All  of  this  testimony  only  gives  us  the  indefinite  knowledge 
that  bile  has  some  important  influence  in  fat-digestion,  but  does 
not  give  us  the  slightest  clue  to  the  manner  in  which  it  exerts  its 
wonderful  influence. 

We  do  not  know  whether  it  assists  in  splitting  the  fats,  or  in 
emulsifying  them,  or  in  promoting  their  absorption,  or  whether 
it  acts  in  some  other  mysterious  manner ;  and  the  contradictory 
statements  of  Westinghausen  "■'  and  Groeper,*  concerning  the  ques- 

1  Arch,  of  Phys.  and  Pathol.,  Paris,  1890. 

2  Archiv  f.  Anat.  u.  Phys.,  1873.  3  Ibid.,  1879. 


B.   K.   RACHFORD.  33. 

tion  whether  or  not  bile  promotes  the  passage  of  fats  through 
animal  membranes,  have  left  us  entirely  at  sea  on  this  important 
point.  In  fact,  our  only  definite  knowledge  concerning  the  action 
of  bile  in  intestinal  digestion  is  that  it  prevents  putrefaction, 
but  what  influence  this  anti-putrefactive  action  of  bile  may  have 
on  fat-digestion  we  do  not  know.  We  may,  therefore,  say  that 
we  are  entirely  ignorant  of  the  manner  in  which  bile  acts  in  pro- 
moting the  intestinal  digestion  of  fats. 

One  fact  is  quite  well  established  in  the  physiology  of  fat- 
digestion,  viz.,  that  splitting  of  fats  is  an  important,  if  not  neces- 
sary, preliminary  step  in  fat-digestion.  But  while  physiologists 
agree  that  the  splitting  of  fats  is  an  important  factor  in  their  di- 
gestion, there  is  a  great  difference  of  opinion  as  to  the  extent  of 
the  splitting  required — some  believing  that  only  sufficient  acid  is 
developed  in  the  fat  to  make  it  emulsible  in  an  alkaline  liquid, 
and  others  that  all  the  fat  must  be  split  into  fatty  acid  and  glycerine 
before  it  can  be  absorbed.  With  this  introduction  we  will  now 
note  the  conclusions  which  1  have  reached  by  my  experiments  (rt-), 
and  then  show  what  application  they  may  have  in  fat-digestion  : 

I.  Heating  neutral  fats  will  develop  in  them  fatty  acid,  and, 
therefore,  make  them  emulsible  in  an  alkaline  liquid.  The  cook- 
ing of  fats  will,  therefore,  by  developing  in  them  fatty  acids, 
assist  in  their  digestion, 

3.  Pancreatic  juice  has  the  property  of  rapidly  splitting  neutral 
fat  into  fatty  acids  and  glycerine.  This  action  is  so  rapid  that  it 
may  develop  5^^  per  cent,  of  fatty  acid  in  seven  minutes,  and  all 
the  fat  may  be  split  into  fatty  acids  and  glycerine  in  less  than  an 
hour.  These  figure  are  taken  from  pancreatic  juice  acting  in  test- 
tubes  at  room  temperature. 

3.  Pancreatic  juice  splits  fats  almost  twice  as  rapidly  at  body 
(37°  ^•)  ^s  ^t  room  (iS°  C.)  temperature.  It  can,  therefore, 
develop  in  neutral  olive  oil  5^  per  cent,  of  fatty  acid  in  four 
minutes,  and  split  all  the  oil  in  half  an  hour. 

4.  Pancreatic  juice  of  the  rabbit  does  not  contain  an  emulsion 
ferment ;  it  does  not  even  furnish  good  conditions  for  giving  an 
emulsion  with  oil  containing  fatty  acid. 

5.  The  presence  of  bile  or  of  a  :^  per  cent,  solution  of  hydro- 
chloric acid,  or  of  both,  not  only  forbids  the  formation  of  emul- 
sions, but  they  also  exercise  a  destructive  influence  on  newly 
formed  emulsions. 

iii 


34  PANCREATIC    DIGESTION. 

6.  An  equal  amount  of  fresh  rabbit's  bile  will,  on  being 
added  to  rabbit's  pancreatic  juice,  greatly  hasten  its  fat-splitting 
action  in  the  ratio  of  three  and  one-fifth  to  one. 

7.  An  equal  quantity  of  a  \  percent,  solution  of  hydrochloric 
acid  will,  on  being  added  to  pancreatic  juice,  retard  its  fat-split- 
ting action  in  the  ratio  of  two-thirds  to  one. 

8.  A  mixture  of  equal  quantities  of  bile  and  a  \  per  cent, 
hydrochloric  acid  solution  will,  on  being  added  in  equal  quan- 
tities to  pancreatic  juice,  greatly  hasten  its  fat-splitting  action  in 
the  ratio  of  four  to  one.  The  bile  not  only  neutralizes  the  retard- 
ing influence  of  the  hydrochloric  acid  on  the  fat-splitting  proper- 
ties of  the  juice,  but  it  really  acts  niore  powerfully  in  hastening 
the  action  of  the  juice  when  in  the  presence  of  this  acid  than  it 
does  when  acting  alone. 

9.  If  one  part  of  pancreatic  juice  be  diluted  with  five  parts 
of  a  ;^  per  cent,  carbonate  of  sodium  solution,  its  fat-splitting 
properties  will  be  greatly  retarded  in  the  ratio  of  one  to  eight, 
and  further  dilution  with  soda  solution  gives  greater  retardation ; 
this  property  of  the  juice  being  practically  destroyed  when  it  is 
ten  times  diluted  with  soda  solution. 

We  may  summarize  from  the  above  propositions  as  follows  : 

a.  Pancreatic  juice  can,  acting  alone,  do  a  certain  piece  of 
w^ork  in  .v  minutes,  viz.,  develop  in  neutral  olive  oil  a  certain 
quantity  of  fatty  acid. 

b.  Pancreatic  juice  acting  in  the  presence  of  five  parts  of  a 
\  per  cent,  solution  of  sodium  carbonate  will  require  eight  x 
minutes  to  do  the  same  work,  and  in  the  presence  of  ten  parts  of 
the  same  soda  solution  its  action  will  be  almost  destroyed. 

c.  Pancreatic  juice  acting  in  the  presence  of  an  equal  quantity 
oi  ii  \  per  cent,  solution  of  hydrochloric  acid  will  require  ^2  •* 
minutes  to  do  the  same  work. 

d.  Pancreatic  juice  acting  in  the  presence  of  an  equal  quan- 
tity of  a  mixture  of  bile  and  a  \  per  cent,  hydrochloric  acid  solu- 
tion will  require  only  \  x  minutes  to  do  the  same  work. 

From  the  last  two  propositions  we  may  make  another  : 

e.  If  bile  be  added  to  pancreatic  juice  which  is  acting  in  the 
presence  of  HCl,  the  fat-splitting  action  of  the  juice  will  be 
hastened  as  one  and  one-half  to  one-fourth,  or  as  six  to  one;  and 
reversely,  if  the  bile  be  cut  off  from  pancreatic  juice  which  has 
previously  been   acting  in  the  presence  of  both  bile  and   hydro- 


B.  K.  RACHFORD.  35 

chloric   acid,  the   fat-splitting   properties  of  the  juice  will   be  re- 
tarded as  six  to  one. 

APPLICATION    OF    THESE    PRINCIPLES    TO    FAT-DIGESTION. 

During  the  process  of  cooking,  as  we  have  seen  (a),  a  con- 
considerable  percentage  of  fatty  acid  is  developed  in  fat,  so  that 
the  fat  in  the  food  passes  into  the  stomach  not  as  neutral,  but  as 
rancid^  fat.  In  the  stomach,  so  far  as  we  know,  the  rancidity 
of  the  fat  is  not  increased,  but  it  is  mixed  with  hydrochloric  acid, 
and,  therefore,  passes  into  the  duodenum  very  much  increased 
in  acidity.  The  contents  of  the  stomach,  as  it  passes  into  the 
duodenum,  contained  \  per  cent,  of  hydrochloric  acid.  The  fat, 
therefore,  enters  the  duodenum  as  part  of  such  an  acid  mixture, 
and  in  such  a  state  is  subjected  to  the  action  of  pancreatic  juice. 

Pancreatic  juice  has  the  property  of  rapidly  splitting  neutral 
fat  into  fatty  acid  and  glycerine  ;  acting  alone  at  room  tempera- 
ture it  can  develop  in  neutral  olive  oil  5^^  per  cent,  of  fatty  acid 
in  seven  minutes,  and  at  body  temperature  it  can  develop  this 
amount  of  acid  in  four  minutes,  and  split  all  the  oil  in  about  half 
an  hour.  This  indicates  the  rapidity  of  action  of  pure  pancreatic 
juice  on  neutral  olive  oil,  but  such  are  not  the  conditions  found 
in  the  duodenum.  The  fat  in  the  duodenum  is  not  subjected  to 
the  action  of  unadulterated  pancreatic  juice,  but  to  pancreatic 
juice  mixed  with  bile.  The  bile  and  pancreatic  juice  are  poured 
through  a  common  opening  into  the  duodenum,  and  are,  there- 
fore, mixed  before  they  come  in  contact  with  the  fat.  Of  great 
physiological  importance,  therefore,  is  the  conclusion  to  which  I 
have  arrived — that  an  equal  quantity  of  bile  will  hasten  the  fat- 
splitting  action  of  pancreatic  juice  as  three  and  one-fifth  to  one. 
The  preliminary  mixing  of  bile  with  pancreatic  juice  enables  the 
juice  to  do  three  and  one-fifth  times  the  work  it  would  otherwise 
do.  It  is  a  fact  here  worthy  of  note,  that  we  have  in  this  expe- 
diting action  of  bile  on  the  fat-splitting  properties  of  pancreatic 
juice  at  least  one  of  the  physiological  reasons  for  the  union  of 
the  bile  and  the  pancreatic  ducts  in  the  carnivora.  It  may  be 
well  here  to  refer  to  the  fact  that  bile  alone  does  not  split  fats  (a). 
Its  action,  therefore,  in  assisting  pancreatic  juice  is  purely  in- 
direct, and  is,  therefore,  the  more  remarkable. 

We  have  in  the  above  an  indication  of  the  rapidity  of  action 

I   Rancid  fat  means  fat  containing  fatty  acid. 


36  PANCREATIC    DIGESTION. 

of  a  mixture  of  bile  and  pancreatic  juice  on  pure  neutral  olive 
oil.  But  such  are  not  the  conditions  found  in  the  duodenum, 
where,  as  we  have  above  stated,  the  fats  are  mixed  with  a  \  per 
cent,  solution  of  hydrochloric  acid.  We  must,  therefore,  see 
what  influence  a  mixture  of  bile  and  hydrochloric  acid  will  have 
on  the  fat-splitting  properties  of  pancreatic  juice,  for  it  is  in  the 
presence  of  such  a  mixture  as  this  that  the  juice  must  act  in  the 
normal  duodenum.  Of  great  physiological  importance,  therefore, 
is  the  conclusion  to  which  I  have  arrived  by  test-tube  experiments 
(a),  that  a  mixture  of  bile  and  hydrochloric  acid  hastens  the  fat- 
splitting  action  of  pancreatic  juice  as  four  to  one.  If  pancreatic 
juice  can,  as  stated  above,  develop  5^  per  cent,  of  fatty  acid  in 
four  minutes,  then  the  same  juice  can  in  the  presence  of  bile  and 
hydrochloric  acid  do  the  same  work  in  one  minute.  Again,  if  pan- 
creatic juice  can,  acting  alone,  split  all  the  oil  into  acid  and  gly- 
cerine in  thirty  minutes,  then  in  the  presence  of  bile  and  hydro- 
chloric acid  it  can  do  the  same  work  in  about  eight  minutes. 

The  above  figures  are  taken  from  test-tube  experiments  (a)  ,  and 
the  fat  used  was  neutral  olive  oil.  Now,  as  I  have  shown  elsewhere 
(a),  olive  oil  is  very  easy  of  decomposition.  The  fat  in  the  food 
is,  therefore,  not,  on  the  average,  as  readily  decomposed  as  olive 
oil,  and  there  must  necessarily  be  many  other  sources  of  error  in 
attempting  to  imitate  the  conditions  found  in  the  intestinal  canal. 

The  above  figures,  therefore,  are  thought  to  be  only  relatively 
and  approximately  correct,  but  it  is  my  belief  that  they  are  suffi- 
ciently accurate  to  indicate  that  the  agencies  acting  in  the  healthy 
duodenum  furnish  the  very  best  known  conditions  for  hastening 
the  fat-splitting  properties  of  pancreatic  juice,  and  chief  among 
these  agencies  are  :  the  body  temperature,  the  presence  of  bile 
and  hydrochloric  acid,  and  the  peristaltic  movements  of  the  duo- 
denum, which  insure  the  mixing  of  its  contents. 

That  fats  are  split  with  great  rapidity  under  the  very  favor- 
able conditions  furnished  by  the  duodenum  is  a  physiological  fact 
of  great  importance,  for  it  is  quite  evident  that  if  this  rate  of  fat- 
splitting  be  continued  as  the  food  passes  down  the  small  intes- 
tine, all  the  fat  would  be  split  into  acid  and  glycerine  long  before 
the  period  required  for  intestinal  digestion.  One  of  two  things 
must  therefore  occur — either  all  the  fat  is  split,  or  some  agency 
exercises  a  retarding  influence  on  the  fat-splitting  process  as  the 
food  passes  down  through  the  intestine  ;  but  I  shall  have  more  to 


B.   K.  RACHFORD.  37 

say  on  this  point  when  we  come  to  study  the  changes  that  occur 
in  fat  after  it  leaves  the  duodenum. 

Let  us  now  inquire  what  influence  the  conditions  furnished 
by  the  healthy  duodenum  would  have  on  the  formation  of  emul- 
sions. I  have  shown  by  my  experiments  i^a)  that  pancreatic 
juice  not  only  does  not  contain  an  emulsion  ferment,  but  that  it 
does  not  even  furnish  good  conditions  for  giving  an  emulsion 
with  oil  containing  fatty  acid.  The  alkali  in  the  juice  seems  to 
be  in  some  combination  which  does  not  readily  allow  it  to  com- 
bine with  the  fatty  acid  to  form  a  soap,  and  this  we  have  seen  (a) 
is  a  necessary  preliminary  step  in  the  formation  of  a  permanent 
emulsion.  But  the  most  important  fact  bearing  on  the  formation 
of  emulsions  in  the  duodenum  is  that  the  agents,  bile  and  hydro- 
chloric acid,  the  most  important  in  furnishing  the  favorable  con- 
ditions for  the  splitting  of  fats,  are  the  very  agents  which  forbid 
the  formation  of  an  emulsion.  An  emulsion  not  only  cannot  form 
in  the  presence  of  bile  and  hydrochloric  acid,  but  these  agents 
actually  destroy  newly  formed  emulsions  {a).  It  seems,  there- 
fore, that  the  conditions  furnished  by  the  normal  duodenum  are 
as  admirably  adapted  to  prevent  emulsion-forming,  as  they  are 
to  promote  fat-splitting.  We  may,  therefore,  in  a  few  words, 
sum  up  the  changes  occurring  in  fats  in  the  duodenum,  viz.  :  fats 
are  rapidly  split,  but  not  emulsified,  in  the  normal  duodenum. 

The  rancid  fat  leaves  the  duodenum,  and  passes  into  the 
jejunum,  and  on  downward  through  the  small  intestine;  there  it 
comes  in  contact  with  the  intestinal  juice  and  other  agents  which 
have  an  influence  on  its  digestion. 

But,  first,  let  us  note  certain  anatomical  conditions  which  may 
have  an  influence  in  fat-digestion.  The  horseshoe  shape  and  the 
comparative  immobility  of  the  duodenum  will  make  the  rate  of 
passage  of  food-stuffs  through  it  comparatively  slow,  and  in  that 
way  contribute  to  the  fat-splitting  by  exposing  for  a  longer  time 
the  fats  to  the  fat-splitting  agencies  acting  under  the  most  favor- 
able conditions.  But  as  the  fats  leave  the  duodenum,  they  pass 
at  once  into  the  larger,  and  more  freely  movable,  descending 
jejunum,  and  their  rate  of  passage  through  this  portion  of  the 
intestine  would  therefore  be  much  more  rapid  than  through  the 
duodenum,  and  the  influence  of  the  bile  and  hydrochloric  acid  on 
the  fat-splitting  properties  of  pancreatic  juice  would  be  rapidly 
lost  in  dilution  with  the  intestinal  contents.     These  anatomical 


38  PANCREATIC    DIGESTION. 

conditions  have  much  more  significance  when  considered  in  the 
light  of  my  observation  (a)  that  five  parts  of  a  :^  per  cent,  car- 
bonate of  soda  solution  will  greatly  retard  the  fat-splitting  pro- 
perties of  pancreatic  juice  in  the  ratio  of  one  to  eight,  and  that 
ten  parts  practically  destroy  this  property ;  since  we  infer  from 
this  that  intestinal  juice  which  contains  this  j'ercentage  of  soda 
will  have  the  same  retarding  influence.  This  retarding  influence 
of  the  intestinal  juice  begins  as  soon  as  the  food  leaves  the  duo- 
denum, and  is  the  more  rapidly  felt  the  more  rapidly  the  food  is 
hurried  along  the  jejunum.  It  would  seem,  therefore,  that  the 
conditions  in  the  small  intestine  below  the  duodenum  are  most  un- 
favorable to  fat-splitting,  and  it  is  probable  that  they  very  greatly 
retard,  if  they  do  not  entirely  check,  the  fat-splitting  process. 

Let  us  now  consider  what  influence  the  conditions  found  in 
the  jejunum  and  ileum  may  have  on  the  formation  of  emulsions, 
and  in  considering  this  question  it  will  be  necessary  to  keep  con- 
stantly in  mind  one  important  fact,  viz.  :  when  rancid  fat  is  mixed 
with  a  \  per  cent,  carbonate  of  soda  solution,  a  good,  permanent 
emulsion  always  results  (ff). 

The  intestinal  mucous  membrane  of  the  jejunum  and  ileum  is, 
during  digestion,  constantly  bathed  with  intestinal  juice,  which 
we  have  before  stated  contains  about  \  per  cent,  of  carbonate  of 
soda.  The  rancid  fat  passing  along  the  intestine  must,  in  being 
absorbed,  come  in  contact  with  this  \  per  cent,  solution  of  carbo- 
nate of  soda  ;  this  being  the  case,  more  or  less  emulsion  would 
necessarily  result,  this  emulsion  occurring  just  at  the  mucous 
surface,  and  probably  just  prior  to  resorption.  This  seems  to 
me  to  be  an  inevitable  conclusion  from  the  conditions  existing  in 
the  small  intestine.  This  explanation  does  not  comprehend  the 
emulsification  of  all  the  fats  in  the  small  intestine,  but  only  such 
a  part  of  it  as,  in  the  process  of  resorption,  passes  through  the 
alkaline  coating  on  the  mucous  membrane.  That  the  fat  in  the 
lumen  of  the  small  intestine  is  often  not  emulsified,  and  that  the 
intestinal  contents  are  sometimes  acid,  argues  nothing  against 
the  above  application  of  existing  facts.  I  do  not  wish  to  express 
the  belief,  however,  that  the  emulsification  of  fats  is  necessary 
to  their  resorption,  for  this  I  do  not  believe.  A  portion  of  the 
fat  may  pass  into  the  villi  in  the  form  of  soluble  soap.  This  is, 
in  fact,  very  probable,  since  in  the  conditions  above  named,  soap- 
formation  is  the  chemical  force  which  produces  the  emulsion. 


B.   K.  RACHFORD. 


39 


Where  the  intestinal  contents  are  very  rancid,  it  is  quite  probable 
that  soap-formation,  independent  of  any  influence  it  may  have 
in  forming  emulsions,  is  an  important  preliminary  step  to  fat-re- 
sorption.  All  I  wish  to  insist  upon  is  that  the  conditions  found 
in  the  intestinal  canal  clearly  indicate  that  emulsion-forming  is 
also  one  of  the  preliminary  steps  to  fat-resorption,  and  I  may 
add  that  to  my  mind  it  is  the  most  important  step. 

Milk  is  a  physiological  emulsion  that  is  absorbed  when  thrown 
into  the  rectum,  and  may  be  taken  and  digested  by  animals  in 
which  both  bile  and  pancreatic  ducts  have  been  ligated.  This  is 
sufficient  proof  that  the  emulsion  of  the  fat  in  milk  is  an  impor- 
tant preliminary  step  to  its  resorption,  and  would  lead  us  to  infer 
that  the  proper  emulsion  of  the  fats  in  the  intestine  would  in  like 
manner  promote  their  absorption.  But  it  is  not  the  purpose  of 
this  paper  to  enter  further  into  the  subject  of  fat-resorption. 
Having  traced  the  fats  through  the  various  stages  of  their  diges- 
tion until  they  are  almost,  if  not  quite,  prepared  for  resorption, 
we  can  return  to  the  consideration  of  certain  interesting  and 
practical  questions,  which  were  omitted  because  they  had  no 
direct  bearing  on   the  question  under  consideration. 

That  hydrochloric  acid  retards  the  fat-splitting  properties  of 
pancreatic  juice  is  a  fact  of  considerable  clinical  and  pathological 
importance,  since  this  retarding  influence  would  be  felt  when  the 
bile  was  shut  off  from  the  intestinal  canal  by  occlusion  of  the 
bile-ducts  from  any  pathological  cause.  We  have  elsewhere  («) 
shown  that  this  retarding  influence  of  hydrochloric  acid  may  be 
represented  by  the  ratio  of  two-thirds  to  one,  and  that  the  expe- 
diting influence  of  bile  in  the  presence  of  hydrochloric  acid  may 
be  represented  by  the  ratio  of  four  to  one.  If,  therefore,  the 
bile  be  shut  off  from  the  intestinal  canal,  its  expediting  influence 
on  the  fat-splitting  properties  of  pancreatic  juice  would  not  only 
be  lost,  but  the  retarding  influence  of  the  hydrochloric  acid  would 
be  felt,  and  the  work  done  by  pancreatic  juice  before  and  after 
the  shutting  off  of  the  bile  would  be  represented  by  the  ratio  of 
four  to  two-thirds,  or  six  to  one.  All  physiologists  agree  that  a 
certain  amount  of  fat-splitting  is  necessary  to  fat-digestion,  and  we 
may,  I  think,  take  for  granted  that  no  unnecessary  fat-splitting 
takes  place  during  normal  digestion.  About  lo  per  cent,  of  fatty 
acid  in  oil  gives  the  best  spontaneous  emulsion  at  body  tempera- 
ture (a),  and  more  or  less  acid  than  this  does  not   give  a  perfect 


40  PANCREATIC    DIGESTION. 

emulsion.  We  infer  from  this  that  about  lo  per  cent,  of  fatty- 
acid  is  developed  in  intestinal  fat  preparatory  to  its  emulsion  and 
resorption.  But  whatever  amount  of  fat-splitting  normally  occurs, 
we  may  be  quite  certain  that  natural  selection  has  provided  the 
conditions  under  which  this  amount  of  fat-splitting  may  take 
place.  For  example,  the  comparative  immobility  of  the  duodenum, 
its  horseshoe  shape,  its  diminution  in  calibre,  and  its  close  attach- 
ment to  the  head  of  the  pancreas — all,  no  doubt,  have  an  influence 
on  the  rate  of  passage  of  food-stuflFs,  and  this  rate,  which  is 
chiefly  controlled  by  these  and  other  anatomical  conditions,  was 
established  to  accord  with  normal  digestive  functions.  By  this 
inechanism  the  fats  are  exposed  to  the  action  of  pancreatic  juice 
just  long  enough  to  allow  for  whatever  action  that  juice  may 
have  in  fat-digestion.  With  these  anatomical  facts  in  mind,  we 
are  better  prepared  to  appreciate  the  important  part  that  bile 
plays  in  the  intestinal  digestion  of  fats.  Let  us  suppose  that 
under  normal  conditions  the  fats  are  exposed  in  the  duodenum  to 
the  action  of  pancreatic  juice  for  x  minutes,  which  time  is  suffi- 
cient for  whatever  fat-splitting  is  necessary  at  this  point.  Now 
if  the  bile  is  cut  off,  the  rate  of  passage  of  the  food-stuffs,  being 
controlled  by  anatomical  conditions,  would  remain  the  same,  and 
the  fats  would  still  be  exposed  to  the  action  of  the  juice  for  only 
X  minutes.  But  since  in  the  absence  of  bile  the  pancreatic  juice 
is  able  to  accomplish  only  one-sixth  of  the  fat-splitting  which  it 
normally  does,  it  would  follow  that  the  fats  would  pass  the  duo- 
denum with  only  one-sixth  of  the  splitting  that  normally  occurs ; 
and  since  the  splitting  of  fats  is  a  necessary  preliminary  step  in 
their  digestion,  it  would  follow  that  the  fats  would  pass  in  great 
part  undigested.  This  gives  to  bile  a  most  important  and  definite 
position  among  the  juices  which  assist  in  fat-digestion,  since  we 
have  here  pointed  out  one  of  the  ways  in  which  it  exerts  its  well- 
known  influence.  We  have  now  an  explanation  of  the  pale,  fatty 
stool  that  occurs  when  the  bile-ducts  are  occluded  from  any  cause. 
The  fatty  stool  will  also  occur  when  the  pancreatic  secretion  is 
shut  off  from  the  intestine,  but  it  should  contain  less  fatty  acid, 
and  not  have  the  paleness  and  putridity  of  the  fatty  stool  due  to 
occlusion  of  the  bile-ducts.  We  should  also  have  fatty  stools 
when  the  intestinal  juice  is  absent  or  deficient  because  of  a  failure 
in  fat-resorption,  and  the  characteristic  of  the  fatty  stool  due  to 
this  cause  would  be  the  large  amount  of  fatty  acid  it  contained. 


Reprinted  from  the  American  yournal  of  Pivsiolo^y,    !'<?/.  A'/,  No.  5, 

July  1,  1899. 


THE  DIASTATIC  ACTION  OF  PANCREATIC 
JUICE. 


In  recent  years  many  observers  have  devoted  much  time  and 
labor  to  the  study  of  the  action  of  unorganized  ferments  on  food- 
stuffs. In  this  study  amylopsin,  the  diastatic  ferment  of  the 
pancreas,  has  been  ahnost  wholly  neglected.  In  fact,  as  far  as  I 
am  aware,  no  systematic  study  of  the  action  of  amylopsin  on 
starch  under  the  various  conditions  herein  described  has  ever 
been  made  with  pure  pancreatic  juice. ^ 

Chittenden,  Langley  and  Eves,  and  others  have  given  us  most 
valuable  information  on  the  diastatic  action  of  saliva  as  modified 
by  various  conditions,  suggested  by  the  conditions  under  which 
diastatic  ferments  are  supposed  to  act  in  the  digestive  tract ;  and 
in  the  absence  of  experimental  work  to  determine  the  diastatic 
action  of  pancreatic  juice,  under  such  varying  conditions,  we 
have  for  the  most  part  been  forced  to  formulate  our  knowledge 
of  the  action  of  amylopsin  from  the  experimental  work  done 
with  ptj'alin  and  other  diastatic  ferments.  It  may  be  that  the 
diastatic  action  of  the  pancreatic  juice  will  under  all  conditions 
be  the  same  as  that  of  saliva;  yet,  however  this  may  be,  there 
can  be  no  doubt  that  it  would  be  more  desirable  to  have  our 
knowledge  of  the  diastatic  action  of  pancreatic  juice  based  upon 
experiments  made  with  the  juice  itself  rather  than  be  forced  to 
infer  the  extent  of  its  action  under  diverse  conditions  from  the 
action  of  other  diastatic  ferments  under  similar  conditions. 

In  this  statement  I  do  not  wish  to  appear  to  underrate  the 
value  of  these  studies  or  to  insist  that  the  principles  of  starch 
digestion,  as  obtained  from  the  study  of  the  diastatic  action  of 
saliva  and  malt,  shall  not  be  applied  in  explaining  the  diastatic 
action  of  pancreatic  juice  in  the  small  intestine,  but  it  goes  with- 

I  See  the  criticism  of  Hamburger,  Archiv.  f.  d.  ges.  Physiol.,  1895, 
Ix,  p.  558. 
41 


42  PANCREATIC    DIGESTION. 

out  saying  that  confirmatory  experiments  made  with  pure  pan- 
creatic juice  would  substitute  certainty  for  inference  and  place 
our  knowledge  of  the  intestinal  digestion  of  starches  on  a  much 
more  satisfactory  footing. 

The  work  of  pancreatic  juice  in  carrying  on  the  intestinal 
digestion  of  starchy  foods  is  recognized  as  a  digestive  function 
second  in  importance  to  none.  That  experimenters  have  neg- 
lected this  field  of  w^ork  is  not  therefore  due  to  its  unimportance, 
but  rather  to  the  difiiculties  in  the  way  of  obtaining  pure  pan- 
creatic juice  in  quantities  sufficient  to  carry  on  a  systematic 
research.  The  purpose,  therefore,  of  this  paper  is  not  only  to 
record  some  experiments,  which  I  recently  have  made,  but  also 
and  more  especially  to  call  attention  to  a  method  of  obtaining 
pure  pancreatic  juice  from  the  rabbit  in  sufficient  quantity  for 
experimental  purposes. 

OPERATION    FOR    TEMPORARY    PANCREATIC    FISTULA 
IX    THE    RABBIT. 

The  operation  for  making  a  temporary  pancreatic  fistula  in 
the  rabbit  was  first  described  by  me  in  the  yournal  of  Physiology., 
1891.  xii,  p.  80.  The  operation  given  here  in  detail  is  an  improve- 
ment on  the  original,  and  makes  it  possible  for  any  observer  to 
obtain  sufficient  pancreatic  juice  for  research.  Experience  has 
taught  me  that  it  is  a  waste  of  time  to  use  any  but  the  largest  and 
strongest  rabbits.  With  such  animals  the  operation  for  temporary 
pancreatic  fistula  is  easily  and  quickly  done  as  follows.  After 
removing  the  hair  make  an  abdominal  incision  in  the  linea  alba, 
on  a  level  with  the  lower  ribs,  three  centimetres  long.  Find  the 
duodenum,  w'hich  is  easily  reached  high  up  in  the  right  hypochon- 
driac region  lying  close  against  the  abdominal  wall,  and  bring  it 
through  this  opening.  Run  down  the  gut  to  a  point  where  the  peri- 
toneum binds  it  so  closely  that  it  will  not  come  through  the 
opening  without  tearing  the  mesenteric  attachment,  and  just  at 
this  point  will  be  found  the  pancreatic  duct  as  it  passes  through 
a  leaf  of  the  pancreas  to  enter  the  intestinal  canal.  Gently  sep- 
arate the  mesenteric  attachment  of  the  gut  so  as  to  bring  the 
latter  through  the  abdominal  opening  without  tearing  blood-ves- 
sels and  producing  unnecessary  hemorrhage.  By  holding  the 
gut  to  the  light  the  pancreatic  duct  can  readily  be  observed  and 
two  points  chosen,  one  on  either  side  about  two  centimetres  from 


B.   K.  RACHFORD. 


43 


the  papilla,  for  applying  ligatures  to  the  intestine.  These  points 
should  be  selected  with  an  eye  to  the  vascular  distribution  to  the 
intestine,  so  that  the  blood-supply  shall  be  disturbed  as  little  as 
possible.  The  ligatures  are  tied  at  this  point  so  as  to  occlude 
the  lumen  of  the  intestine  ;  the  ends  are  then  passed  around  the 
body  of  the  animal  and  tied  in  that  position.  If  it  be  preferred 
small  clamps,  resembling  prepuce  clamps,  may  be  used  instead 
of  ligatures.  AH  of  the  intestines  except  that  portion  included 
between  the  clamps  or  ligatures  is  returned  to  the  abdominal 
cavity  xvithout  section.  This  arrangement  will  maintain  the  rela- 
tive position  of  the  parts,  so  that  the  portion  of  the  mesentery 
holding  the  pancreatic  duct  cannot  be  disarranged  by  peristaltic 
contractions  or  by  the  subsequent  movements  of  the  animal.  If 
a  large  abdominal  wound  is  made  it  is  sometimes  necessary  to 
close  it  partially  by  stitches,  so  that  the  intestine  cannot  be  forced 
through  the  opening  and  in  that  way  disarrange  the  parts.  Care 
must  be  taken,  however,  that  the  abdominal  wound  be  sufficiently 
open  to  permit  the  free  passage  of  the  niesentery  carrying  the 
pancreatic  duct.  The  portion  of  the  intestine  included  between 
the  clamps  or  ligatures  is  now  laid  open  opposite  its  mesenteric 
attachment  and  spread  out  on  the  abdominal  wall.  The  lateral 
margins  are  packed  with  absorbent  cotton  to  prevent  bleeding. 
The  pancreatic  papilla  can  be  observed  on  the  exposed  mucous 
membrane.  In  a  short  time  it  will  open  and  pancreatic  juice 
will  exude.  Into  this  papilla  is  inserted  a  small  glass  cannula  to 
which  has  been  attached  an  inch  or  two  of  rubber  tubing.  The 
cannula  being  in  position,  the  exposed  mucous  membrane  is  cov- 
ered with  absorbent  cotton,  which  may,  if  necessary,  be  saturated 
from  time  to  time  with  warm  physiological  salt  solution.  The 
flow  of  juice  may  begin  at  once,  or  it  may  not  commence  for  an 
hour  after  the  insertion  of  the  tube.  When  the  pancreatic  juice 
commences  to  flow  it  continues  from  five  to  eight  hours.  During 
this  time  the  juice  is  collected  by  emptying  the  filled  cannula  from 
time  to  time  and  reinserting  it.  In  this  manner  may  be  obtained 
from  three  to  five  c.c.  of  pancreatic  juice  uniform  and  powerful 
in  physiological  action.  It  is  my  custom  to  have  two  rabbits 
under  operation  at  the  same  time,  and  in  this  way  I  never  fail  to 
obtain  juice  sufficient  for  an  experiment.  The  pancreatic  juiee 
collected  from  both  rabbits  is  mixed  together  in  a  single  tube 
and  afterward  divided  equally  between  the  tubes  containing  the 


44  PANCREATIC    DIGESTION. 

digestive  mixtures.  In  this  way  one  is  sure  tliat  all  the  tubes  of 
a  single  experiment  contain  pancreatic  juice  uniform  in  physio- 
logical action, 

INFLUENCE    OF    BILE    AND    HYDROCHLORIC    ACID    ON    THE 
DIASTATIC    ACTION    OF    PANCREATIC    JUICE. 

In  the  starch  experiments  here  recorded  the  bile  used  was 
obtained  from  the  same  rabbits  that  furnished  the  pancreatic 
juice. 

The  method  used  in  determining  the  rate  of  diastatic  action 
was  the  one  described  by  Pavy  ^  under  the  title  "Quantitative 
Determination  of  Sugar  by  the  Ammoniated  Cupric  Test." 

The  time  of  each  experiment  was  forty-five  minutes.  When 
the  diastatic  action  was  stopped  by  boiling  the  mixtures,  the  total 
volume  of  liquid  in  each  tube  was  60  c.c.  One  gram  of  wheat 
starch  boiled  in  a  definite  quantity  of  water  was  used  in  each. 

The  hydrochloric  acid  used  in  these  experiments  was  in  the 
form  of  a  o.  I  per  cent,  solution.  I  made  a  number  of  tests  to 
determine  the  amount  of  this  acid  solution  necessary  to  neutralize 
a  given  quantity  of  pancreatic  juice  and  the  results  of  these  tests 
are  noted  elsewhere  in  this  paper.  Determinations  were  also 
made  by  Dr.  W.  H.  Crane,  who  was  given  5  minims  of  pure 
pancreatic  juice  and  a  sample  of  the  o.  i  percent,  hydrochloric 
acid  solution  used  in  the  experiments,  with  the  request  that  he 
estimate  the  amount  of  the  acid  solution  necessary  to  neutralize 
the  5  minims  of  juice. 

Dr.  Crane  diluted  the  pancreatic  juice  with  5  c.c.  of  distilled 
water  and  added  a  drop  of  0.5  per  cent,  alcoholic  solution  of 
dimethyl  amido  azo-benzol.  Ten  c.c.  of  o.i  per  cent,  hydrochloric 
acid  were  diluted  to  100  c.c,  placed  in  a  burette,  and  added  drop 
by  drop  to  the  pancreatic  juice.  Neutralization  Avas  obtained 
with  4.5  c.c.  of  the  o.oi  per  cent,  hydrochloric  acid.  Thus  5 
minims  of  pancreatic  juice  required  0.45  c.c.  of  o. i  per  cent, 
hydrochloric  acid  for  neutralization. 

It  may  here  also  be  noted  that  all  the  hydrochloric  acid  tubes, 
in  the  above  or  in  subsequent  experiments,  contained  frorn  2  to 
10  c.c.  of  the  hydrochloric  acid  solution  in  excess  of  the  amount 
required  to  neutralize  the  pancreatic  juice,  and  that  the  subse- 
quent addition  of  bile  or  albumen  was  not  sufficient  to  neutralize 
I   Pavy,  F.  W. :   "Physiology  of  the  Carbohydrates,"  London,  1894. 


B.   K.  RACHFORD. 


45 


this  excess  of  free  acid.  All  hydrochloric  acid  tubes  therefore  in 
the  following  experiments  except  those  to  which  sodium  carbo- 
nate was  added  contained  free  acid. 

I  submitted  to  Dr.  Crane  a  fluid  containing  the  following 
ingredients:  pancreatic  juice  lo  minims,  o.  i  per  cent,  hydro- 
chloric acid  solution  3  c.c,  starch  i  gram,  water  25  c.c,  with 
the  request  that  he  determine  whether  or  not  the  fluid  contained 
free  acid,  and  if  acid  how  much  bile  would  be  required  to  neu- 
tralize the  acid. 

Dr.  Crane  found  27.4  c.c.  of  fluid  in  the  test-tube.  It  was 
acid  to  dimethyl  amido  azo-benzol.  Of  the  starchy  fluid  13.7  c.c. 
were  placed  in  a  beaker  and  bile  (0.9  c.c.  of  which  had  been 
diluted  to  9.0  c.c.  with  water)  introduced  from  a  graduated 
pipette.  Neutralization  required  6.2  c.c.  Thus  27.4  c.c.  of  the 
fluid  are  neutralized  by  1.24  c.c.  bile. 

I  would  call  attention  to  the  fact  that  the  mixture  upon  which 
the  above  report  was  made  was  taken  as  a  sample  of  the  hydro- 
chloric acid  tubes  in  the  experiments  on  page  46.  It  must  be 
noted,  however,  that  this  mixture  contained  the  minimum  amount 
of  acid  used  in  any  of  the  digestive  mixtures,  and  that  this  mix- 
ture was  found  to  require  1.24  c.c.  of  bile  to  neutralize  it;  a 
much  larger  amount  of  bile  than  was  used  in  any  of  the  tubes, 
except  tubes  i  and  2  of  Experiment  VII. 

In  these  tubes,  however,  it  will  be  noted  that  the  8  and  10  c.  c. 
of  the  hydrochloric  acid  solution  which  these  tubes  respectively 
contained  was  suflicient  to  give  to  them  an  acid  reaction. 

Studying  the  following  experiments,  it  is  plain  that  bile 
slightly  expedites  the  diastatic  action  of  pancreatic  juice.  The 
expediting  influence  of  the  bile,  however,  is  here  shown  to  be  so 
slight  that  the  manner  of  its  action  scarcely  merits  discussion.  It  is 
important  to  observe  that  the  bile  does  not  exert  an  unfavorable 
influence  on  the  diastatic  action  of  pancreatic  juice.  But  it  is  of 
much  more  importance  to  note  that  theo.  i  per  cent,  hydrochloric 
acid  solution  used  in  these  experiments  had  only  a  slight  retarding 
influence  on  the  diastatic  action  of  the  ferment.  A  slight  retarda- 
tion is,  however,  seen  in  every  case.  Tube  3  in  each  of  these 
experiments  contains  3  c.c.  of  a  o.  i  per  cent,  solution  of  hydro- 
chloric acid,  which  gave  to  the  contents  a  decided  acid  reaction. 
In  experiments  made  to  determine  the  amount  of  the  hydrochloric 
acid   solution    necessary   to    neutralize    pancreatic    juice,    it    was 


46 


PANCREATIC    DIGESTION. 


Experiment. 


Pancreatic 
juice. 

Miniins. 


Water, 
c.c. 


percent. 
HCl. 


Bile. 
Minims. 


Sta 
Gn 


ch. 

ni. 


Starch 
converted. 

Per  cent. 


I. 

I 

3 

3 

4 

II. 
I 

2 

3 

4 

Ill 
I 

2 

3 

4 

IV, 
I 

2 

3 

4 

V. 

I 

2 

3 

4 

VI 
I 

2 

3 

4 


lO 
lO 
lO 


lO 
lO 


lO 
lO 
lO 
lO 

7 
7 
7 

7 


lO 
lO 
lO 


lO 
lO 
lO 
lO 


6o 

57 
57 
6o 

6o 

57 
57 
6o 

6o 

57 
57 
6o 

6o 

57 
57 
6o 

6o 

57 
=7 
6o 

6o 

57 
57 
6o 


30 
27 
23 
30 

50 

50 
37 
40 

32 
32 
20 

25 

25 
27 
24 
26 


34 
36 
30 
34 

34 
36 
24 
28 


found  that  12  to  15  minims  of  the  hydrochloric  acid  solution 
would  destroy  the  alkalinity  of  10  minims  of  pancreatic  juice, 
and  that  15  to  18  minims  would  give  to  it  an  acid  reaction. 
Hence  the  amount  of  hydrochloric  acid  solution  in  these  tubes 
was  more  than  2  c.c.  in  excess  of  the  amount  required  to  neutral- 
ize the  alkalinity  of  the  pancreatic  juice,  and  yet  in  the  presence 
of  this  excess  of  free  hydrochloric  acid  the  pancreatic  juice  had 
almost  as  much  diastatic  action  as  it  had  when  acting  alone  in 
the  presence  of  its  own  alkaline  salts. 

Of  yet  greater  interest  are  the  tubes  marked  2  in  the  above 
experiments.  Each  of  these  tubes  contained  not  only  3  c.c.  of 
the  hydrochloric  acid  solution,  but  also  a  certain  amount  of  bile. 
A  study  of  these  tubes  shows  us  that  the  bile  not  only  neutralized 
the  slight  retarding  influence  of  the  free  hydrochloric  acid,  but 


B.   K.  RACHFORD. 


47 


also  furnished  the  conditions  in  the  presence  of  this  acid  for  pan- 
creatic juice  to  do  its  most  rapid  diastatic  work.  The  tubes  con- 
taining both  bile  and  pancreatic  juice,  in  every  experiment  except 
one,  lead  in  the  amount  of  diastatic  work  done.  In  the  experi- 
ment in  which  the  bile  and  hydrochloric  acid  tube  fails  to  do  the 
most  v.^ork,  the  failure  is  probably  due  to  the  small  amount  of 
bile  used.  Whatever  may  be  the  explanation,  it  is  an  important 
physiological  fact  that  bile,  when  added  to  pancreatic  juice  acting 
in  the  presence  of  a  small  quantity  of  free  hydrochloric  acid,  will 
not  only  neutralize  the  retarding  influence  which  the  free  acid 
has  on  the  diastatic  action  of  pancreatic  juice,  but  will  in  doing 
so  furnish  the  most  favorable  conditions  for  the  action  of  this 
ferment.  And  it  is  also  important  to  note  that  bile  will  accom- 
plish this  result  without  neutralizing  the  acid  completely,  thus 
showing  that  the  favorable  influence  of  the  bile  on  the  diastatic 
action  of  pancreatic  juice  is  not  simply  one  of  acid  neutralization. 
The  following  experiment  shows  even  more  clearly  the  value 
of  bile  when   pancreatic  juice  is  acting  in   the  presence  of  free 


EXPERIMENT    VII. 


1  Pancreatic 
1      juice. 
I    Minims. 

Water, 
c.c. 

3.1  percent. 
HCl. 
c.c. 

Bile. 

Minims. 

Starch. 
Gram. 

Starch 
reduced. 
Per  cent. 

I. 

12 
12 
12 
12 
12 

^2 
48 
48 

60 

8 

12 

12 

8 

0 

20 

30 

0 

0 

0 

I 

40 

24 
12 

14 
30 

2 

X 

4. 

hydrochloric  acid.  Here  the  retarding  influence  of  8  and  I3  c.c. 
of  a  0.1  per  cent,  hydrochloric  acid  solution  is  very  marked,  but 
in  tube  i,  containing  8  c.c.  of  the  hydrochloric  acid  solution,  20 
minims  of  bile  not  only  neutralizes  the  retarding  action  of  the 
hydrochloric  acid,  but  also  enables  the  pancreatic  juice  to  do  even 
more  diastatic  work  than  is  done  in  tube  5,  where  the  pancreatic 
juice  is  acting  apart  from  the  influence  of  either  hydrochloric 
acid  or  bile.  In  tube  2,  30  minims  of  bile  enables  12  minims  of 
pancreatic  juice  acting  in  the  presence  of  i3  c.c.  of  hydrochloric 
acid  solution  to  digest  24  per  cent,  of  starch  instead  of  12  per 
cent.,  the  amount  digested  in  tube  3,  in  which  the  same  quantity 
of  pancreatic  juice  acted  in  the  presence  of  13  c.c.  of  the  hydro- 
chloric acid  solution  without  the  assistance  of  the'  bile. 


48 


PANCREATIC    DI(;ESTI0N. 


In  Experiment  VIII,  even  more  f^raphically  than  in  any  that 
has  preceded  it,  is  shown  the  retarding  influence  of  free  hydro- 
chloric acid  on  the  diastatic  action  of  pancreatic  juice  and  the 
value  of  bile  in  neutralizing  this  retarding  action.  Here  12  c.c. 
of  the  hydrochloric  acid  solution  almost  destroys  the  diastatic 
action  of  15  minims  of  pancreatic  juice,  and  8  c.c.  of  the  acid 
solution  greatly  retards  its  action,  while  7  minims  of  bile  is  suffi- 
cient to  neutralize  entirely  the  retarding  influence  of  8  c.c.  of 
the  acid  solution. 

EXPERIMENT    VIII. 


Pancreatic 

juice. 

Minims. 


Water, 
c.c. 


0.1  percent. 
HCI. 


Bile. 

Minims. 


Starch. 
Gram. 


Starch 
reduced. 


2 
-^ 
4 

5 
6 

7 
8 

9 


15 
15 
15 
15 
15 


60 

^2 
48 
52 
48 

52 

48 

52 
48 


o 

8 
12 

8 
12 

8 
12 

8 
12 


25 

14 

2 

26 


5 

25 
6 


The  preceding  experiments  clearly  establish  the  fact  that  bile 
is  not  necessary  to  the  diastatic  action  of  pancreatic  juice  acting 
alone  uninfluenced  by  hydrochloric  acid,  but  that  bile  may  be  of 
the  greatest  assistance  to  pancreatic  juice,  indeed  almost  neces- 
sary to  its  full  diastatic  action,  when  the  former  is  acting  in  the 
presence  of  free  hydrochloric  acid,  and  that  bile  can  serve  this 
purpose  without  neutralizing  all  of  the  free  acid  present. 


INFLUENCE    OF    ACID    ALBUMEN    ON    THE    DIASTATIC 
ACTION    OF    PANCREATIC    JUICE. 

In  Experiment  IX,  the  egg  albumen  was  mixed  with  the 
hydrochloric  acid  solution  before  the  pancreatic  juice  was  added 
to  the  tube,  and  here  it  will  be  seen  that  0.3  gram  of  g^^^  albumen 
exercised  very  much  the  same  influence  on  pancreatic  juice  acting 
in  the  presence  of  free  hydrochloric  acid  that  the  bile  did  in  the 
previous  experiments.  Tubes  2,  4  and  6  demonstrate  that  acid 
albumen  very  materially  expedites  the  diastatic  action  of  pancre- 
atic juice.  Tubes  6,  7  and  8  of  this  experiment  contain  each  10 
minims  of  bile.  In  tube  6  the  presence  of  the  bile  seems  to  add 
little  to  the  diastatic  action  of  the  pancreatic  juice,  since  almost 


B.   K.  RACHFORD. 


49 


the  same  percentage  of  starch  is  digested  in  tubes  2  and  4,  which 
do  not  contain  bile,  but  in  other  respects  resemble  tube  6.  In 
tube  7,  however,  we  learn  by  comparison  with  tubes  3  and  5  that 
the  10  minims  of  bile  had  a  very  decided  influence  in  increasing 
the  diastatic  action  of  the  pancreatic  juice  in  the  conditions  under 
which  it  is  acting.      In  tube  7  of  this  experiment  0.3  gram  of  egg 

EXPERIMENT    IX. 


Pancreatic 

juice. 

Minims. 

Water, 
c.c. 

0.1  percent. 
HCl. 
c.c. 

Egg 
Allnimen. 

Gram. 

Bile. 
Minims. 

Starch. 
Gram. 

Starch 
reduced. 
Per  cent. 

I 

2 

3 

4 

5 

6 

7 

8 

10 
10 
10 
10 
10 
10 
10 
10 

60 
56 
S2 
56 

t;2 
55 
52 
60 

0 

4 
8 

4 
8 

4 
8 
0 

0 
0.3 

0-3 

0.3 

0-3 

0.3 

0 

0 

0 

0 

0 

0 

10 

10 

10 

23 
31 
19 

37 
15 
38 
25 
25 

albumen  was  not  sufficient  to  neutralize  fully  the  retarding  action 
of  8  c.c.  of  the  hydrochloric  acid  solution  ;  the  addition  of  10 
minims  of  bile,  however,  accomplished  this.  The  failure  of  bile 
to  increase  further  the  diastatic  action  of  pancreatic  juice  in  tube 
6  is  due  to  the  fact  that  the  0.3  gram  of  egg  albumen  is  almost  if 
not  quite  suflicient  to  neutralize  the  4  c.c.  of  hydrochloric  acid 
solution,  and  for  this  reason  the  further  addition  of  bile  or  egg 
albumen  would  not  materially  increase  the  action  of  the  pancre- 
atic juice. 


INFLUENCE    OF    SODIUM    CARBONATE    ON    THE    DIASTATIC 
ACTION    OF    PANCREATIC    JUICE. 

Experiment  X  was  planned  for  the  purpose  of  studying  the 
influence  of  sodium  carbonate  on  the  diastatic  action  of  pancre- 
atic juice  acting  under  various  conditions.  A  i  per  cent,  solution 
of  sodium  carbonate  was  used.  Tubes  2  and  3  of  this  experiment 
show  that  2  and  5  c.c.  of  the  sodiuin  carbonate  solution  almost 
entirely  destroy  the  diastatic  action  of  5  minims  of  pancreatic 
juice ;  while  tubes  4  and  5  show  that  5  minims  of  bile  have  a 
decided  influence  in  neutralizing  the  retarding  influence  which 
the  soda  solution  has  upon  tlie  diastatic  action  of  pancreatic  juice. 
Tubes  6  and  7  indicate  that  the  0.6  gram  of  egg  albumen  also  had 
some  influence  in  neutralizing  the  retarding  action  of  the  soda. 


50 


PANCREATIC    DIGESTION. 


EXPERIMENT    X. 


Pancreatic 
juice. 

Water. 

I  per  cent. 
NajCOg. 

Bile. 

Albumen. 

0.1  percent. 
HCl. 

Starch. 

Starch 
reduced. 

Minims. 

c.c. 

c.c. 

Minims. 

Gram. 

c.c. 

Gram. 

Per  cent. 

I.. 

.^ 

6o 

0 

0 

0 

0 

50 

2.. 

5 

58 

2 

0 

0 

0 

7 

3 

5 

55 

5 

0 

0 

0 

2 

4 

5 

58 

2 

5 

0 

0 

15 

S- 

5 

55 

5 

5 

0 

0 

6 

6 

5 

58 

2 

0 

0.6 

0 

10 

7- 

5 

55 

5 

0 

0.6 

0 

4 

8. 

5 

52 

5 

0 

0.6 

3 

13 

If  hydrochloric  acid  be  added  to  a  mixture  in  which  pancre- 
atic juice  is  acting  on  starch  in  the  presence  of  sodium  carbonate 
the  acid  will  neutralize  the  retarding  influence  of  the  alkali. 
This  is  shown  in  tube  8,  This  action  may  be  simply  one  of 
chemical  neutralization,  but  whatever  the  explanation,  the  obser- 
vation is  interesting  as  showing  that  the  diastatic  power  of  pan- 
creatic juice  in  a  strongly  alkaline  mixture  may  be  increased  by 
the  addition  of  a  small  quantity  of  hydrochloric  acid. 


EXPERIMENT    XI. 


Pancreatic 

juice. 

Minims. 

Water, 
c.c. 

0.1  percent. 

NajCOg. 

c.c. 

Bile. 

Minims. 

Starch. 
Gram. 

Starch 
reduced. 
Per  cent. 

I 

4 
4 
4 
4 
4 

60 

58 
SS 
58 
55 
60 
60 

0 

2 

5 
2 

5 
0 

0 

0 
0 
0 

4 
4 
4 
4 

50 

5 

3 

II 

13 

8 

2 

3 - 

4 

c  

6.  . 

17 

8 

Experiment  XI  again  demonstrates  the  destructive  action  of 
sodium  carbonate  on  the  diastatic  action  of  pancreatic  juice,  and 
also  shows  the  value  of  bile  in  neutralizing  this  retarding  influ- 
ence. In  tubes  6  and  7  it  is  shown  that  bile  itself  has  some  dias- 
tatic power. 

CONCLUSIONS. 

1.  A  small  quantity  of  free  hydrochloric  acid  has  little  or  no 
retarding  influence  on  the  diastatic  action  of  pancreatic  juice. 

2.  Larger  quantities  of  free  hydrochloric  acid  very  materially 
retard  the  diastatic  action  of  pancreatic  juice  :  in  one  experiment 
12  c.c.  of  a  0.1  per  cent,  solution  of  hydrochloric  acid  almost  de- 


B.   K.  RACHFORD.  51 

stroyed  the  diastatic  action  of  15  minims  of  pancreatic  juice 
acting  in  a  mixture  of  60  cubic  centimetres  volume ;  in  anotiier 
experiment  the  same  quantity  of  acid  reduced  by  two-thirds  the 
diastatic  action  of  12  minims  of  pancreatic  juice.  The  facts  that 
different  specimens  of  pancreatic  juice  vary  in  their  degree  of 
alkalinity  and  in  their  diastatic  power  make  it  impossible  to  for- 
mulate precise  statements  concerning  the  influence  which  definite 
quantities  of  acid  will  have  on  definite  quantities  of  pancreatic 
juice. 

3.  Acid  proteids  in  small  quantities  slightly  increase  the 
diastatic  action  of  pancreatic  juice.  Neutral  proteids,  therefore, 
when  added  to  pancreatic  juice  acting  in  the  presence  of  free 
hydrochloric  acid  will  not  only  neutralize  the  retarding  action  of 
the  acid  on  the  diastatic  action  of  the  juice,  but  they  will  also  by 
the  formation  of  acid  albumen  assist  materially  the  pancreatic 
juice  in  its  work. 

4.  Sodium  carbonate  has  a  very  destructive  influence  on  the 
diastatic  action  of  pancreatic  juice.  Two  cubic  centimetres  of  a 
I  per  cent,  solution  of  sodium  carbonate  almost  totally  destroys 
the  diastatic  action  of  5  minims  of  pancreatic  juice  acting  in  a 
mixture  of  60  cubic  centimetres  volume. 

5.  Bile  has  no  retarding  influence  on  the  diastatic  action  of 
pancreatic  juice  ;  in  fact,  it  slightly  expedites  its  action. 

6.  Bile  not  only  neutralizes  the  retarding  influence  which  free 
hydrochloric  acid  has  upon  the  diastatic  action  of  pancreatic 
juice,  but  in  the  presence  of  free  hydrochloric  acid  it  very  mate- 
rially expedites  the  action  of  the  juice.  Here  again  it  is  impos- 
sible to  formulate  rules  as  to  the  exact  amount  of  bile  necessary 
to  neutralize  the  retarding  influence  of  a  definite  quantity  of 
hydrochloric  acid,  and  thus  give  to  a  definite  quantity  of  pancre- 
atic juice  its  greatest  diastatic  power.  In  the  above  experiments, 
however,  it  will  be  seen  that  four  to  eight  minims  of  bile  were 
sufficient  to  neutralize  the  retarding  influence  of  from  four  to 
eight  cubic  centimetres  of  a  o.  i  per  cent,  hydrochloric  acid  solu- 
tion without  destroying  the  acid  reaction  of  the  mixture  and  thus 
to  give  to  pancreatic  juice  its  greatest  diastatic  power. 

7.  Bile  has  a  marked  influence  in  diminishing  the  retarding 
influence  which  sodium  carbonate  has  upon  the  diastatic  action 
of  pancreatic  juice. 

8.  Bile  itself  has  some  diastatic  power. 


52  PANCREATIC    DIGESTION. 

Not  the  least  interesting  point  in  these  conclusions  is  the 
suggestion  that  bile  may  play  a  not  unimportant  part  in  the  in- 
testinal digestion  of  starches.  If  there  be  any  free  acid  in  the 
food,  as  it  is  discharged  from  the  stomach  into  the  duodenum, 
the  bile  will  neutralize  this  acid  and  thereby  assist  the  acid  pro- 
teids  discharged  with  the  starches  through  the  pylorus,  in  fur- 
nishing the  most  favorable  conditions  for  the  diastatic  action  of 
pancreatic  juice.  And  possibly  of  even  more  importance  is  the 
fact  that  bile  will  limit  the  destructive  action  of  sodium  carbon- 
ate on  the  diastatic  action  of  amylopsin. 

In  conclusion,  I  wish  to  express  my  thanks  to  Dr.  Frank 
Southgate,  who  has  assisted  me  very  greatly  in  the  arduous  de- 
tails of  these  experiments. 


Reprinted  from  the  yournal  of  Physiology ,   Vol,  XXV,  No.  2. 
November  28,  1899. 


IV —INFLUENCE  OF  BILE,  OF  ACIDS,  AND  OF  ALKA- 
LIES ON  THE  PROTEOLYTIC  ACTION 
OF  PANCREATIC  JUICE. 


Dr.  Southgate  and  I  published,  in  1895,  the  results  of  some 
experiments  on  the  influence  of  bile  and  combined  hydrochloric 
acid  upon  the  proteolytic  action  of  pancreatic  juice.'  These  re- 
sults have  been  questioned,  by  Chittenden  and  Albro,'-  on  the 
ground  that  similar  results  are  not  obtained  when  pancreatic  ex- 
tracts are  used  in  the  place  of  pancreatic  juice.  It  is  perhaps 
hardly  necessary  to  point  out  that  experiments  with  pancreatic 
extracts  cannot  be  taken  as  decisive  as  to  what  will  happen  when 
pancreatic  juice  is  employed.  Nevertheless,  in  view  of  the  posi- 
tion taken  by  Chittenden  and  Albro,  I  have,  with  the  aid  of  Dr. 
Southgate,  made  further  experiments  on  the  subject. 

METHOD. 

All  the  pancreatic  juice,  employed  in  these  experiments,  was 
obtained  from  rabbits  by  a  method  devised  by  me  and  first  pub- 
lished in  this  journal,  xii,  p.  72,  1S91,  and  recently  improved  and 
published  in  detail  in  the  Ajncricafi  Journal  of  Physiology .,  ii, 
p.  483,  1899. 

The  bile,  used  in  all  of  these  experiments,  was  fresh  rabbits' 
bile  taken  from  the  same  animals  which  furnished  the  pancreatic 
juice,  and  in  nearly  ail  of  the  experiments  it  was  filtered  before 
using. 

The  proteid  employed  was  purified  and  dried  blood  fibrin 
prepared  by  washing  with  water,  extracting  with  cold  and  boil- 
ing alcohol,  and  lastly  with  ether.  It  was  then  ground  to  a  fine 
powder,  dried  and  weighed  at  100°  C.  All  of  the  weighings 
vp^ere  made  by  a  competent  assistant  and  the   powders  were  de- 

1  Medical  Record,  1895,  P-  878. 

2  ^niericqin  'Journal  of  Physiology,  i,  p.  307,  1898. 
53 


54  PANCREATIC    DIGESTION. 

livered  to  me  along  with  carefully  weighed  and  marked  filter 
papers.  At  the  close  of  each  experiment  the  filter  papers,  con- 
taining the  undigested  residues  of  fibrin,  were  dried  and  weighed 
at  loo^  C.  and  the  result  sent  to  me.  The  assistant  who  did  the 
weighing  knew  nothing  of  the  contents  of  the  digestion  tubes  or 
returned  filter  papers.  This  precaution  was  taken  for  the  pur- 
pose of  avoiding  such  slight  errors  as  might  unconsciously  occur 
from  a  knowledge  of  the  contents  of  the  weighings.  The  diges- 
tive mixtures,  used  in  these  experiments,  were  placed  in  test-tubes 
of  large  calibre,  especially  prepared  for  this  purpose,  which  were 
kept  in  a  water  bath  at  38°  C.  They  were  equally  stirred  while 
the  digestive  process  was  going  on.  At  the  close  of  the  experi- 
ment the  undigested  residues  were  collected  on  weighed  and 
marked  filters,  and  after  being  thoroughly  washed  were  delivered 
to  the  assistant  to  be  dried  and  weighed  as  previously  described. 

The  experiments  recorded  in  this  paper  were,  as  a  rule,  com- 
menced by  the  collection  of  the  pancreatic  juice  about  eight  o'clock 
in  the  morning,  so  that  by  three  o'clock  in  the  afternoon  from 
three  to  four  c.c.  of  pancreatic  juice  would  be  obtained.  During 
this  time  the  pancreatic  juice,  from  the  two  or  three  rabbits 
operated  upon,  was  placed  in  a  common  receptacle  and  kept  in  a 
cool  place.  The  juice  was  equally  divided  between  the  digestion 
tubes  of  one  or  more  experiments.  This  insured  the  relative 
accuracy  of  the  results,  since  each  digestion  mixture  of  an  experi- 
ment contained  the  same  quantity  of  pancreatic  juice  uniform  in 
physiological  action.  Corresponding  tubes  of  different  experi- 
ments, however,  cannot  be  compared  because  of  the  variation  in 
strength  of  the  different  specimens  of  pancreatic  juice. 

The  digestion  experiments  were  commenced  about  four  o'clock 
in  the  afternoon  and  continued  until  about  eleven  o'clock  at  night. 
The  filter  papers  containing  the  undigested  residues  of  fibrin  were 
placed  in  the  oven  about  midnight ;  in  some  experiments  earlier, 
in  others  later.  It  will  thus  be  seen  that  an  experiment  required 
from  seventeen  to  eighteen  hours  of  constant  watching. 

I  am  not  prepared  to  say  that  experiments  made  with  pan- 
creatic juice,  collected  under  the  above  conditions,  are  more  re- 
liable than  those  made  with  pancreatic  extracts.  Yet  I  fail  to 
see  why  results  obtained  from  natural  pancreatic  juice  do  not 
constitute  a  method  more  nearly  resembling  the  conditions  under 
which  proteolysis  takes  place  in  the  duodenum  ;  and  further  than 


B.   A'.   RACHFORD.  55 

this  it  occurs  to  me  that  if  the  fresh  bile  and  pancreatic  juice  of 
the  same  animal  be  commingled  in  the  digestion  of  fibrin  the 
conditions  would  even  more  closely  resemble  pancreatic  proteoly- 
sis as  it  occurs  in  the  carnivora. 

In  some  comparative  anatomy  studies,"  made  in  1891,  I  called 
attention  to  the  fact  that  the  more  exclusively  carnivorous  the 
animal  the  more  certainly  will  the  bile  and  pancreatic  juice  be 
poured  into  the  duodenum  through  a  common  opening,  and  the 
more  closely  will  this  opening  approach  the  pylorus.  In  the  lion 
this  opening  is  only  6  cm.  from  the  pylorus  ;  in  the  tiger  ^  cm.  ; 
in  the  leopard  4  cm.  ;  in  the  wild  cat  3  cm.  ;  and  in  a  number  of 
other  carnivora  this  distance  is  less  than  2  cm.  In  a  few  animals 
such  as  the  bear,  the  badger,  and  the  fox,  there  is  an  apparent 
exception  to  the  above  rule.  In  these  animals,  however,  although 
the  ducts  do  not  have  a  common  opening,  they  enter  the  duode- 
num almost  upon  the  same  level,  so  that,  by  this  arrangement, 
the  bile  and  pancreatic  juice  are  mixed  directly  they  are  poured 
into  the  intestines. 

That  this  preliminary  mixing  of  bile  and  pancreatic  juice  so 
near  the  pylorus  in  carnivorous  animals  serves  a  physiological 
purpose  cannot  be  doubted,  and  it  seems  very  improbable  that 
this  purpose  is  served  solely  in  connection  with  fat  digestion'  and 
without  reference  to  the  far  more  important  proteid  digestion  in 
these  animals. 

However  this  inay  be,  this  arrangement  suggests  that  the  ideal 
method  of  studying  pancreatic  proteolysis  as  it  takes  place  in  the 
carnivora,  is  one  that  uses  the  pure  juice  and  the  fresh  bile  of  the 
same  animal,  and  subjects  them  to  preliminary  mixing  before  they 
are  brought  into  contact  with  proteids.  This  suggestion  has 
even  more  importance  when  one  remembers,  as  Chittenden  and 
Albro  have  so  clearly  noted,  "how  radically  bile  from  different 
species  of  animals  differs  in  composition." 

When  rabbit's  bile  is  used  with  rabbit's  pancreatic  juice,  we 
are  imitating  conditions  which  nature  has  evolved  for  the  diges- 
tion of  food-stuffs  in  the  small  intestine  of  this  animal.  It  would 
seem,  therefore,  that  results  obtained  by  this  method  would  be  of 
value  in  assisting  to  interpret  the  digestive  processes  normally 
going  on  in  the  intestine  of  man.     Surely  such  experiments  can- 

1  Medicine ,  December,  1895. 

2  This  journal,  xii,  p.  73,  1891. 


56 


PANCREATIC    DIGESTION. 


not  be  less  valuable  than  those  obtained  from  pancreatic  extracts 
commingled  with  the  bile  of  different  species  of  animals. 


Table  A. — Influence  of  Bile  on  the  Proteolytic  Action  of 
Pancreatic  yuice. 


Number  of  ex 
periment. 

I 

II 

Ill 

IV 

V _.. 

VI 

VII 

VIII 

IX 

X 

XI 

XII 


Duration 
in  hours. 


Fibrin  in 
grams. 


Water  in 
c.c. 


Bile  in 
c.c. 


Pancreatic 

juice  in 


Loss  of 

weight  in 

grams. 


■398 

•399 
•399 

.400 
.400 
.400 

.400 
.400 
.400 

.400 
.400 
.404 

.400 
.400 
.400 

.400 
.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.407 
.402 
.407 

.402 
.401 
.401 

.400 
.400 


10 
10 
10 

6 
6 
6 

7 
7 
7 

10 
10 
10 

7 
7 

7 

6 
6 
6 

6 
6 

7 
7 

6 
6 

10 
10 
10 

10 
10 
10 

6 
6 


o 
•369 
•369 


.246 
.246 

o 

.184 

.184 


.184 

o 

.184 

o 

.184 

o 

.184 

o 

•369 
■369 

o 

•369 
•369 

o 

.184 


.246 
.246 
.246 

.246 
.246 
.246 

.246 
.246 
.246 

■369 
•369 
•369 

•431 
•431 
■431 

.492 
.492 
.492 

.616 
.616 

.616 
.616 

.616 
.616 

.677 
.677 
.677 

•739 
•739 
•739 

■1%9 
•739 


.06 1 

•093 
.089 

•075 
•  lo.i; 
.096 

.065 
.097 
.089 

.078 
.091 
.109 

.146 
.158 
.179 

.097 
.130 

.127 

.146 
.187 

.096 

.122 

•"3 
.130 

.070 

.087 
.079 

.098 

•134 
.123 

.130 
.178 


INFLUENCK    OF    BILK    ON    THE    PROTEOLYTIC    ACTION    OF 
PANCREATIC    JUICE. 

Chittenden  and  Albro  conclude,  "  That  the  addition  of  fresh 
bile  to  a  neutral  pancreatic  extract  does  not  give  rise  to  any  great 


B.   K.  RACHFORD. 


57 


degree  of  stimulation,  i.e.,  tlie  proteid  digesting  power  of  the 
enzyme  is  not  remarkably  increased."  And  they  further  add 
that,  "in  no  one  of  our  experiments  do  we  find  a  confirmation 
of  the  results  reported  by  Rachford  and  »Southgate,  who  found  on 
an  average  that  the  proteolytic  action  of  pancreatic  juice  was 
increased  one-fourth  by  the  addition  of  bile." 

As  the  preceding  table  will  show,  I,  on  the  other  hand,  am 
unable,  working  with  pancreatic  juice,  to  confirm  the  results,  as 
to  the  impotency  of  bile,  which  Chittenden  and  Albro  obtained 
w^orking  with  pancreatic  extracts. 

An  examination  of  this  table  clearly  demonstrates  that  when 
fresh  rabbits'  bile  is  added  to  fresh  rabbits'  pancreatic  juice, 
acting  upon  neutral  fibrin,  the  proteolytic  power  of  the  juice  will 
be  markedly  stimulated,  and  in  most  of  the  experiments  the  juice 
is  able  to  do  one-fourth  more  work  by  reason  of  the  presence  of 
the  bile. 

INFLUENCE    OF    BILE    ON     PROTEOLYSIS    CARRIED    ON 
BY    ORGANIZED    FERMENTS. 

In  the  following  table  I  have  grouped  a  series  of  experiments 
in  which  the  digestive  process  was  allowed  to  go  on  for  tw^elve  or 
more  hours.  The  putrid  odor,  vrhich  developed  in  all  of  these 
tubes,  showed  that  organized  ferments,  along  with  the  trypsin, 
were  taking  part  in  the  proteolysis.  While  these  experiments 
have  no  value  in  the  study  of  pancreatic  proteolysis,  yet  when 
the  results  obtained  from   this  series  are  compared   with  those 

Table  B. — htfiuence  of  Bile  on  Proteolysis  Carried  on  by 
Organized  Fermejtts, 


Number  of  ex- 
periment. 


II. 


III. 


IV. 


Duration 
in  hours. 


14 

14 
14 

12 
12 
12 

12 
12 


Fibrin  in 
grams. 

.400 
.400 

•397 
.400 
.406 

.398 
.400 

■399 

.389 
•399 


Water  in 
c.c. 


10 
10 
10 


10 

10 


10 
10 


Bile  in 
c.c. 


•554 

o 

•369 
•3^ 

o 

.862 
.862 

o 

•369 


Pancreatic 

juice  in 

c.c. 

•369 
•369 

.616 
.616 
.616 

.862 
.862 
.862 

.924 
•924 


Loss  of 

weight  in 

grams. 

.172 
■151 

.ri8 
.091 
.096 

.129 
•125 
.129 

•139 
.146 


58  PANCREATIC    DIGESTION. 

obtained  from  a  study  of  Table  A,  one  is  led  to  conclude  that 
bile  has  an  influence  in  limiting  or  retarding  the  fermentation 
which  is  carried  on  by  organized  ferments.  In  only  one  of  these 
experiments,  No.  IV,  do  we  find  the  bile  tube  doing  more  pro- 
teolytic work  than  the  tube  in  which  the  pancreatic  juice  acted 
without  the  influence  of  bile.  In  Experiment  III  the  bile  tubes 
and  the  non-bile  tube  do  practically  the  same  work,  while  in 
Experiments  I  and  II,  which  lasted  fourteen  hours,  we  find  that 
the  pancreatic  juice  acting  alone  does  more  proteolytic  work 
than  it  does  when  acting  in  the  presence  of  bile.  The  inference 
seems  plain  that  in  the  fourteen-hour  experiments  the  bile  was 
able  to  so  limit  bacterial  action  that  the  pancreatic  tubes  con- 
taining no  bile  were  able  to  do  the  most  proteolytic  work.  I  am 
therefore  of  the  opinion  that  rabbits'  bile,  while  it  expedites  the 
fermentation  carried  on  by  the  pancreatic  enzyme,  trypsin  retards 
the  albuminous  fermentations  carried  on  by  organized  ferments. 
This  view  seems  to  favor  the  opinion  that  bile  by  limiting  bacte- 
rial action  may  act  as  an  intestinal  antiseptic. 

INFLUENCE    OF    COMBINED     HYDROCHLORIC    ACID    UPON    THE 
PROTEOLYTIC    ACTION    OF    PANCREATIC    JUICE. 

In  the  following  experiments  the  degree  of  saturation  of  the 
fibrin  was  estimated  from  careful  experiments,  made  expressly 
to  detemine  the  point  of  saturation  of  the  fibrin  used  in  these 
experiments,  with  the  carefully  tested  hydrochloric  acid  solution 
here  employed.  The  presence  or  absence  of  free  hydrochloric 
acid  was  determined  by  a  0.5  per  cent,  alcoholic  solution  of 
dimethyl-amido  azo-benzol. 

Chittenden  and  Albro  state  that  "the  combined  or  free  acid 
which  passes  from  the  stomach  through  the  pylorus  is  without 
doubt  quickly  removed  by  absorption  or  destroyed  by  neutraliza- 
tion." And  that,  "  the  evidence  is  certainly  in  favor  of  the  view 
that  the  contents  of  the  duodenum  are  generally  alkaline."  Apart 
from  this  statement  of  Chittenden  and  Albro  I  have  not  been 
able  to  find  any  evidence  pointing  to  alkalinity  of  the  contents 
of  the  duodenum  in  the  carnivora.  At  what  part  of  the  intesti- 
nal canal  in  carnivorous  animals  its  contents  cease  to  be  acid  and 
take  on  an  alkaline  reaction  does  not  appear  in  their  paper,  nor  is 
this  matter  made  clear  by  the  research  of  Moore  and  Rockwood,^ 

I  This  journal,  ixi,  p.  373,  1897. 


B.  K.  RACHFORD.  59 

which  they  quote,  as  offering  the  best  evidence  of  the  early  disap- 
pearance of  acid  in  the  upper  portion  of  the  small  intestine.  All 
the  evidence,  in  fact,  which  these  authors  present  leads  to  the 
inference  that  in  carnivorous  animals  fed  on  proteids  the  "  upper 
portion"  of  the  small  intestine  is  usually  acid  and  the  ''lower 
portion  "  is  faintly  alkaline.  These  results  they  obtained  from 
the  dog  and  cat,  the  only  carnivora  upon  which  they  operated. 
And  I  may  add  that  these  views  are  in  accord  with  those  gener- 
ally accepted  by  physiologists  to-day. 

The  experiments  recorded  in  the  tables  which  follow  were 
planned  with  the  purpose  of  studying  the  influence  which  these 
conditions  would  have  on  the  proteolytic  action  of  pancreatic 
juice.  In  this  table  the  "degree  of  saturation,"  refers  to  the 
condition  of  the  fibrin  before  the  pancreatic  juice  was  added. 
In  none  of  the  tubes,  except  one  of  Experiment  XVI,  was  there 
any  free  acid  present. 

By  a  study  of  Experiments  I  to  XII  inclusive,  we  are  led  to 
believe  that  fibrin  one-half  saturated  with  hydrochloric  acid, 
is  as  readily  acted  upon  by  pancreatic  juice  as  is  neutral  fibrin. 
The  amount  of  proteolysis  that  occurred  in  the  tubes  containing 
hydrochloric  acid  will  be  found  almost,  if  not  quite,  to  equal 
that  which  took  place  in  the  tubes  where  pancreatic  juice  was 
acting  upon  neutral  fibrin. 

If,  however,  we  study  Experiments  XIII,  XIV,  XV,  XVI 
and  XVII,  we  find  that  when  the  fibrin  was  nine-tenths  saturated 
with  hydrochloric  acid  the  proteolytic  power  of  pancreatic  juice 
was  considerably  retarded.  In  Experiment  XVI  we  also  note 
the  more  marked  influence  v/hich  free  acid  had  in  retarding  the 
proteolytic  action  of  pancreatic  juice. 

The  results  of  these  experiments  differ  radically  from  those 
of  Chittenden  and  Albro,  who  found  "  that  even  a  few  thousands 
of  I  per  cent,  of  combined  hydrochloric  acid  sufficed  to  exert  an 
inhibitory  influence  on  proteolysis,  and  with  a  sufficient  amount 
of  combined  acid  alone  proteolysis  may  be  almost  completely 
checked."  My  own  experiments,  however,  lead  to  the  conclusion 
that  when  rabbits'  pancreatic  juice  is  added  to  fibrin,  one-half 
saturated  with  hydrochloric  acid,  it  will  do  almost  as  much  work 
in  proteolysis  as  when  added  to  neutral  fibrin.  When,  however, 
the  fibrin  is  nine-tenths  saturated  with  hydrochloric  acid  the  pro- 
teolytic action  of  the  juice  is  retarded.     And  Experiment  No. 


6o 


PANCREATIC    DIGESTION. 


XVI  indicates   that  a   certain  amount  of  pancreatic  proteolysis 
may  go  on  even  in  the  presence  of  free  hydrochloric  acid. 

Table  C. — Influence  of  Combined  HCl  on  the  Proteolytic  Action  of 
Pancreatic  yuice. 


Number  of  ex 
periment. 

I 

II 

Ill 

IV 

V 

VI 

VII 

VIII 

IX 

X 

XI 

XII 

XIII  

XIV 

XV 

XVI 

XVII 


Duration 
in  hours. 


4^ 
4i 


7 
7 

7 
7 

64 
61 

6 
6 


14 
14 
H 

12 
12 


F"ibrin  in 
grams. 

.398 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

.400 
.400 

■398 
.400 

•389 
.401 

.400 

•399 

.400 
.400 
.400 
.400 

•384 
.401 


Degree  of 
saturation. 


free  acid 


Water  in 
c.c. 

7 
7 

7 
7 

6 
6 

7 
7 


6 
6 

10 
10 

10 
10 


10 
10 


10 
10 


Pancreatic 

juice  in 

c.c. 

•246 
.246 

.246 
.246 

.246 
.246 

•309 

•3*^9 

•369 
•369 

•431 
•431 

.492 
.492 

•554 
•554 

.616 
.616 

.616 
.616 

.616 
.616 

•739 
•739 

.246 
.246 

.246 
.246 

•369 
•369 

•369 
•369 
•369 
•369 

.924 
.924 


Loss  of 

weiglit  in 

grams. 

.114 
.105 

.065 
•073 

.065 
•073 

.217 
.225 

.T46 
.162 

.130 
.179 

.121 
.121 

.097 
.031 

•"3 
•"3 

.146 
.105 

.096 
•"3 

.130 
.162 

.161 

•057 

.074 
•045 

.047 

•055 
.172 

•157 
.163 
.191 

,    •139, 
.III 


B.  K.  RACHFORD.  6i 


INFLUENCE    OF     BILE     AND    COMBINED     HYDROCHLORIC     ACID    ON 
THE     PROTEOLYTIC    ACTION    OF    PANCREATIC    JUICE. 

In  these  experiments  "  the  degree  of  saturation  "  refers  to  the 
condition  of  the  fibrin  before  the  bile  and  pancreatic  juice  are 
brought  into  contact  with  it.  That  is  to  say,  I  have  attempted 
to  study  the  influence  which  definite  quantities  of  bile  and  pan- 
creatic juice  would  have  upon  fibrin  one-third,  one-half,  seven- 
tenths,  and  nine-tenths,  saturated  with  hydrochloric  acid.  In 
none  of  the  digestion  tubes  of  this  table  was  there  any  free  acid. 

In  studying  the  following  table  one  notes  that  in  experiments 
from  I  to  V  inclusive  0.5  grams  of  fibrin,  one-third  saturated 
with  hydrochloric  acid,  were  delivered  to  definite  quantities  of 
bile  and  pancreatic  juice,  and  that  in  every  instance  slightly  more 
work  was  done  in  the  tubes  containing  acid  fibrin  than  in  those 
in  which  neutral  fibrin  was  acted  upon  by  pure  pancreatic  juice 
apart  from  the  influence  of  bile  and  combined  hydrochloric  acid. 

On  further  examination  of  this  table  one  is  struck  with  the 
fact  that  in  the  twelve  experiments  from  VI  to  XVII  inclusive, 
0.4  grams  of  fibrin,  one-half  saturated  with  hydrochloric  acid, 
were  delivered  to  definite  quantities  of  bile  and  pancreatic  juice, 
and  that  here  again  the  greatest  amount  of  proteolysis,  in  all 
except  three,  took  place  in  the  tube  in  which  the  bile  and  pan- 
creatic juice  were  acting  upon  acid  proteids. 

Again,  referring  to  the  table,  one  finds  that  the  four  experi- 
ments, from  XVII  to  XXI,  show  a  slight  decrease  in  proteolysis 
in  the  tubes  containing  fibrin  seven-tenths  saturated  with  hydro- 
chloric acid. 

In  the  last  seven  experiments  embraced  in  the  above  table,  an 
effort  was  made  to  study  the  influence  of  definite  quantities  of  bile 
and  pancreatic  juice  acting  upon  fibrin  nine-tenths  saturated.  Of 
these  seven  experiments  the  combined  hydrochloric  acid  retarded 
the  proteolytic  action  of  the  pancreatic  juice  in  all  but  one.  Yet 
the  retardation  in  most  of  these  experiments  was  not  very  great. 

A  careful  examination  of  this  table  does  not  enable  me  to 
agree  with  Chittenden  and  Albro,  that  "combined  acid  alone 
tends  to  retard  pancreatic  proteolysis,  and  the  addition  of  bile 
to  such  mixtures  increases  still  further  the  extent  of  retardation." 
On  the  other  hand,  I  am  led  to  the  conclusions  that  a  small  quan- 
tity of  combined   hydrochloric   acid,   not   greater   than   one-half 


62 


PANCREATIC    DIGESTION. 


Table  D. — Influence  of  Bile  and  Combined  Hydrochloric  Acid  on  the 
Proteolytic  Action  of  Pancreatic  Juice. 


Number 
of  experi- 
ment. 

Duration 
in  hours. 

Fibrin  in 
grams. 

Degree  of 
saturation 
with  HCl. 

Water 
in  c.c. 

Bile 
in  c.c. 

Pancreatic 

juice  in 

c.c. 

Loss  of 

weight  in 

grams. 

I 

4i 
4i 

.501 
.502 
.500 

0 

1 
3 
1 
3 

20 
20 
20 

0 
.616 
.6x6 

.246 
.246 
.246 

•054 
.068 
.069 

II 

4l 
4i 
4l 

•502 

.501 
.502 

0 

1 
3 

20 
20 
20 

0 
.616 
.616 

•309 
•309 
•309 

.076 
.088 
•095 

Ill 

4 
4 

.500 

.500 

0 

1 
3 

6 

6 

0 
.123 

•369 
•369 

.082 
.086 

IV 

4l 

.502 
.500 

0 

1 
3 

20 
20 

0 
616 

.492 
.492 

.083 
.078 

V 

\\ 
4l 

.500 
.500 

.500 
•500 

0 

1 
3 

\ 

1 
3 

7 
7 
7 
7 

0 
369 
•369 
369 

.677 
.677 
.677 
.677 

.092 
.104 
.094 
.092 

VI 

7 

7 

.400 
.400 

n 

1 
2 

6 
6 

0 

.184 

.246 
.246 

.065 
.130 

VII 

8 
8 

.400 
.400 

0 

1 

7 
7 

0 

.184 

.246 
.246 

.065 
.130 

VIII 

7 

7 

.400 
.400 

0 

J. 
2 

7 

7 

0 

.184 

•309 
•309 

.217 
.240 

IX 

6i 
6i 

.400 
.400 

0 

1 
a 

7 
7 

0 

.184 

•369 
•3'9 

.146 
.146 

X 

6 
6 

.400 
.400 

0 

1 
2 

7 

7 

0 

.184 

■431 
•431 

.130 
•195 

XI 

4i 
4i 

.400 
.400 

0 

1. 

7 
7 

0 

.184 

■43' 
•431 

.114 
.127 

XII 

8 
8 

.400 
.400 

n 

6 
6 

0 

.184 

.492 
.492 

.121 
.097 

XIII 

8 

8 

.400 
.400 

0 

1 

6 
6 

0 

.184 

•554 

■554 

.097 

.178 

XIV 

4 

4 

.400 
.400 

0 

J 

7 
7 

0 

.184 

.616 
.616 

.096 
.066 

XV 

6 
6 

.400 
.400 

0 

1 

6 
6 

0 

.184 

.616 
.616 

•"3 
.146 

B.   K.  RACHFORD. 


63 


Table  D. — {^Continued.) 


Number 
of  experi- 
ment. 

Duration 
in  hours. 

Fibrin  in 
grams. 

Degree  of 
saturation 
with  HCI. 

Water 
in  c.c. 

Bile 
in  c.c. 

Pancreatic 

juice  in 

c.c. 

Loss  of 

weight  in 

grams. 

XVI 

6 
6 

.400 
.400 

0 

1 
2 

6 
6 

0 

.184 

.616 
.616 

.146 
•195 

XVII 

6 
6 

.400 
.400 

0 

J 
2 

6 
6 

0 

.184 

•739 
•739 

.130 
.194 

XVIII.. 

42 

4i 

4i 

.500 
.500 
.500 

0 

I'o 

20 
20 
20 

0 
•616 
.616 

.246 
.246 
.246 

.054 
.058 
.050 

XIX 

4i 
4i 
41 

.500 
.500 
.500 

0 

i'o 

1% 

20 
20 
20 

0 
.616 
.616 

•309 
•309 
•309 

.076 
.061 
.067 

XX 

4 
4 
4 

.500 
.500 
.300 

0 

i'b 

20 
20 
20 

0 
.616 
.616 

•369 
•369 
•369 

.082 
.081 
.078 

XXI 

4l 
4l 
4^ 
\\ 

.500 
.500 
.500 
.500 

0 

i'o 

7 
7 
7 
7 

0 

•739 
•739 
•739 

.677 

.677 
.677 

•677 

.092 
.077 
.078 
.076 

XXII 

14 

14 
14 

.400 
.400 
.400 

0 

h 
9 

in 

10 
10 
10 

0 
•369 
•369 

•309 
•309 
•309 

•138 
.101 
.102 

XXIII 

14 

.400 
.400 
.400 

0 

i'o 
9 
1  0 

10 
10 
10 

0 
•554 
•554 

•369 
•  369 
•369 

.172 
.126 
.119 

XXIV 

8 
8 
8 

.400 
.400 
.400 

0 

h 

10 
10 
10 

0 
.246 
.246 

•369 
•369 
•369 

.078 

.088 
.088 

XXV 

14 
14 
14 

.400 
.400 
.400 

0 

h 

10 
10 
10 

0 
•369 
•369 

.616 
.616 
.616 

.irS 
.051 
.056 

XXVI... 

8 
8 

8 

.400 
.400 
.400 

0 

h 

10 
10 
10 

0 
•569 
•569 

.677 

•677 
.677 

.070 
.050 
.056 

XXVII. 

12 
12 
12 

,400 
.400 
.400 

0 

l"i) 

10 
10 
10 

0 

.862 
.862 

.862 
.862 
.862 

.129 
.114 
.100 

XXVIII 

12 
12 

.400 
.400 

0 

h 

10 
10 

0 
•369 

.924 
.921 

•139 
.090 

64 


PANCREATIC    DIGESTION. 


saturation,  will  but  slightly  diiiiinish  the  proteolytic  action  of 
rabbits'  pancreatic  juice,  and  that  when  rabbits'  bile  is  added  to 
these  mixtures  an  increase  in  proteolysis  is  attained. 

My  experiments  indicate,  however,  that  when  hydrochloric 
acid  is  present  in  such  quantities  as  to  more  than  half  saturate 
the  fibrin  it  somewhat  retards  the  proteolytic  action  of  pancreatic 
juice,  even  though  bile  be  present,  and  still  greater  retardation 
occurs  with  increasing  quantities  of  hydrochloric  acid.  Nine- 
tenths'  saturation  considerably  retards  but  by  no  means  destroys 
the  proteolytic  action  of  pancreatic  juice. 

INFLUENCE    OF    BILE    AND    FREE    HYDROCHLORIC    ACID    ON    THE 
PROTEOLYTIC    ACTION    OF    PANCREATIC    JUICE. 

The  study  of  this  question  is  attempted  in  the  following 
table.  In  all  the  experiments  included  in  this  table  the  acid 
tubes  contained  free  hydrochloric  acid,  even  after  the  bile  and 
pancreatic  juice  were  added,  and  a  number  of  these  tubes,  as 
will  be  seen,  contained  acid  far  in  excess  of  the  amount  required 
to  neutralize  the  bile  and  pancreatic  juice  and  saturate  the  fibrin. 
The  acid  determinations  were  made  with  0.5  per  cent,  alcoholic 
solution  of  dimethyl-amido  azo-benzol. 


Table  E. — Influence  of  Bile  and  Free  Hydrochloric  Acid  on  the 
Proteolytic  Action  of  Pancreatic  Juice. 


Number 
of  experi- 
ment. 

Duration 
in  hours. 

Fibrin 

in 
grams. 

HCl. 

in 
grams. 

Water 
in 
c.c. 

Bile 
in 
c  c. 

Pancreatic 

juice  in 

c.c. 

Re- 
action. 

Loss  of 

weight  in 

grams. 

I 

II 

Ill 

8 

8 

14 
14 
14 
14 
14 

4| 
4l 
4l 

4| 
4^ 
4j 
4J 

14 
14 

.502 
•499 

.400 
.400 
.400 
.400 
.400 

.400 
.400 
.400 

.500 
.500 
.500 
.500 

.400 
.400 

0 
.007 

0 
.007 
.007 
.010 
.014 

0 
.007 
.007 

0 
.007 
.007 
.007 

0 
.007 

10 
10 

10 
10 
10 
TO 
10 

20 
20 
20 

20 
20 
20 
20 

10 
10 

0 
••^69 
•369 
•369 
•369 

0 
.616 
.616 

0 
.616 
.616 
.616 

0 
0 

184 
184 

309 
309 
309 
309 
309 

309 
309 
309 

309 
309 

309 
309 

369 
369 

Acid. 

Acid. 
Acid. 
Acid. 
Acid. 

Acid. 
Acid. 

Acid. 
Acid. 
Acid. 

Acid. 

.083 
.019 

.108 
.085 
.084 
.080 
.036 

.098 

IV 

.0.9 
.049 

.076 

V 

.041 

■037 
.047 

.172 

.091 

B.  K.  RACHFORD.  65 

In  every  acid  tube  of  the  five  experiments  here  recorded  a 
marked  retardation  in  proteolysis  occurred,  but  in  none  of  them 
was  the  proteolytic  power  of  the  pancreatic  juice  wholly  de- 
stroyed. In  most  of  the  tubes  the  amount  of  work  done  by  the 
bile  and  pancreatic  juice,  acting  upon  fibrin  supersaturated  with 
hydrochloric  acid,  was  almost  half  as  great  as  that  done  by  pure 
pancreatic  juice  acting  upon  neutral  fibrin.  Under  the  condi- 
tions, therefore,  noted  in  the  above  experiments  free  hydrochloric 
acid  will  greatly  inhibit,  but  will  not  wholly  destroy,  the  pro- 
teolytic action  of  rabbits'  pancreatic  juice,  acting  in  the  presence 
of  rabbits'  bile  upon  blood  fibrin. 

INFLUENCE     OF     SODIUM     CARBONATE     UPON     THE     PROTEOLYTIC 
ACTION    OF    DILUTE    SOLUTIONS    OF    PANCREATIC    JUICE. 

By  reference  to  the  preceding  tables  it  can  readily  be  seen 
that  the  proteolytic  action  of  pancreatic  juice  is  greatly  weak- 
ened by  dilution.  That  is  to  say,  the  most  proteolytic  work,  as 
a  rule,  was  done  in  those  tubes  which  contained  the  largest  quan- 
tities of  pancreatic  juice  and  the  smallest  quantities  of  water,  and 
the  least  amount  of  proteolytic  work  was  done  in  those  tubes 
which  contained  the  smallest  amounts  of  juice  and  the  largest 
amounts  of  water. 

Upon  theoretical  grounds  this  would  seem  to  be  a  serious 
drawback  to  thorough  proteolysis  in  the  intestinal  canal,  since 
this  process  requires  hours  for  its  completion,  and  occurs  not 
alone  in  the  duodenum,  but  probably  throughout  the  greater 
portion  of  the  small  intestine. 

These  inferences  and  deductions  naturally  suggest  an  inquiry 
into  the  influence  which  the  sodium  carbonate  and  alkaline  intes- 
tinal contents  of  the  lower  ileum  and  jejunum  would  have  upon 
the  proteolytic  action  of  pancreatic  juice.  The  few  experiments 
in  the  following  table  w^ere  designed  to  study  this  question. 

The  favorable  influence  w'hich  sodium  carbonate  has  on  the 
proteolytic  action  of  dilute  solutions  of  pancreatic  juice  is  here 
shown.  This  influence  is  most  marked  in  Experiment  II,  wherein 
we  have  the  fact  clearly  demonstrated  that  sodium  carbonate  will 
stimulate  dilute  pancreatic  juice  to  increased  proteolytic  work. 

I  do  not  wish,  however,  to  convey  the  idea  that  sodium  car- 
bonate has  this  power  only  in  dilute  solutions  of  pancreatic  juice. 
I  did  not  study  the  influence  of  sodium  carbonate  on  the  proteo- 


66 


PANCREATIC    DICESTION 


Taislk   F. — In fiiirtir,'  of  Sodium  Carb')nate  on  the  Pvotcolvtic  Action 
of  Dilute  Solutions  of  Pancreatic  Juice. 


Number 
of  experi- 
ment. 

Duration 
in  hours. 

Fibrin  in 
grams. 

Sodium 
carbonate 
in  grams. 

Water 
in  c.c. 

Bile 
in  c.c. 

Puncreatic 

juice  in 

c.c. 

Loss'  of 

weight  in 

grams. 

I  

4i 

.501 

0 

20 

0 

.246 

•0.ii4 

4i 

■50,1 

.050 

20 

0 

.246 

.065 

4i 

•505 

.100 

20 

0 

.246 

.068 

4i 

.501 

.050 

20 

.616 

.246 

.078 

4i 

.501 

.100 

20 

.616 

.246 

.062 

II 

4i 

.502 

0 

20 

0 

■309 

.076 

4i 

•505 

.050 

20 

0 

•^09 

.127 

4i 

.508 

.100 

20 

0 

•309 

•  133 

^\ 

.501 

.050 

20 

.6r6 

•309 

.120 

4I 

•50  + 

.100 

20 

.616 

•309 

•  125 

Ill 

4i 

4| 

.502 
•50+ 

0 

20 

0 

.492 
.492 

.083 

.092 

.025 

20 

.616 

4| 

.500 

.050 

20 

.616 

.492 

.088 

4| 

•505 

.025 

20 

0 

.492 

.096 

4| 

•505 

.050 

20 

0 

•492 

•093 

4l 

.506 

.100 

20 

0 

.492 

.097 

lytic  action  of  pancreatic  juice  under  other  conditions  than  those 
named  in  this  table,  and  have,  therefore,  limited  my  conclusions 
to  its  influence  on  dilute  solutions  of  the  juice. 

From  all  the  evidence,  presented  in  this  paper,  I  am  led  to 
believe  that  the  conditions  which  prevail  throughout  the  entire 
small  intestine  in  carnivorous  animals  are  favorable  to  the  pro- 
teolytic action  of  pancreatic  juice.  In  these  animals  when  the 
proteid  food,  partially  saturated  with  hydrochloric  acid,  is  dis- 
charged from  the  pylorus,  it  at  once  comes  in  contact  with  the 
mixture  of  bile  and  pancreatic  juice,  and  immediately  the  trypsin 
finds  itself  under  conditions  most  favorable  for  its  proteolytic 
action.  These  conditions  prevail  for  a  short  time  only,  when 
the  pancreatic  juice,  more  or  less  weakened  by  dilution,  as  it 
passes  down  the  intestinal  canal,  is  called  upon  to  act  in  the 
presence  of  sodium  carbonate  in  the  lower  and  alkaline  portion 
of  the  ileum  ;  and  here  again  we  find  these  conditions  very  favor- 
able for  the  proteolytic  enzyme  of  the  pancreas.  If  the  above 
conditions,  as  assumed,  be  correct,  then  throughout  the  entire 
small  intestine,  trypsin  finds  itself  under  conditions  more  favor- 
able to  its  proteolytic  action  than  if  it  were  acting,  throughout 
the  canal,  upon  neutral  fibrin  in  neutral  solution. 


ReJ>rinte(f  from  Medicine,  Alav,  1900. 


V— PANCREATIC    DIGESTION    FROM    THE   STAND- 
POINT OF  THE  COMPARATIVE  ANATOMY 
OF  THE  BILE  AND  PANCREATIC 
DUCTS    IN   MAMMALS. 


In  1891  I  published  a  paper  in  the  yournal  of  Physiology  on 
"  The  Influence  of  Bile  on  the  Fat-Splitting  Properties  of  Pan- 
creatic Juice."  In  this  paper  I  demonstrated  the  important 
physiological  fact  that  rabbits'  bile  expedites  the  fat-splitting 
properties  of  rabbits'  pancreatic  juice  in  the  ratio  of  three  to  one. 
Reasoning  by  analogy  from  these  experiments,  I  concluded  that 
when  the  fresh  bile  of  any  animal  is  mixed  with  the  fresh  pancre- 
atic juice  of  the  same  animal  it  will  enable  the  pancreatic  juice  to 
split  fats  much  more  rapidly  than  if  the  juice  were  acting  alone. 
If  this  inference  be  true  it  follows  (since  fat-splitting  is  a  neces- 
sary preliminary  step  in  fat-digestion)  that  all  animals  which 
have  a  common  opening  for  their  bile  and  pancreatic  ducts  are, 
by  reason  of  this  anatomical  arrangement,  much  better  endowed 
for  the  digestion  of  fats  than  those  animals  which  do  not  have  a 
common  opening  for  these  ducts.  For  these  reasons  one  would 
expect  to  find,  in  all  animals  taking  a  quantity  of  fat  in  their 
food,  such  anatomical  conditions  as  would  provide  for  the  pre- 
liminary mixing  of  bile  and  pancreatic  juice  before  they  com- 
menced the  work  of  fat-digestion. 

In  the  same  paper  I  further  demonstrated  that  if  fresh  rabbits' 
bile  be  added  to  fresh  rabbits'  pancreatic  juice,  acting  in  the 
presence  of  a  0.25  per  cent,  solution  of  hydrochloric  acid,  the 
bile  not  only  neutralizes  the  retarding  influence  of  the  hydro- 
chloric acid  on  the  fat-splitting  properties  of  pancreatic  juice,  but 
it  also  acts  more  powerfully  in  hastening  this  action  of  pancreatic 
juice  when  it  is  combined  with  the  hydrochloric  acid  than  it  does 
when  acting  alone.  If  this  physiological  fact  may  be  applied  to 
the  study  of  fat-digestion  in  other  animals,  then  one  may  infer 
67 


68  PANCREATIC    DKiESTION. 

that  the  pancreatic  digestion  of  fats  in  all  animals  is  promoted  by 
the  presence  of  bile  and  a  small  percentage  of  hydrochloric  acid. 
Following  this  argument  one  is  led  to  conclude  that,  in  animals 
taking  a  large  quantity  of  fat  in  their  food,  the  bile  and  pancre- 
atic juice  should  not  only  be  poured  into  the  duodenum  through 
a  common  opening,  but  this  common  opening  should  be  near  the 
pylorus  so  as  to  provide  for  the  mixing  of  the  bile  and  pancreatic 
juice  with  the  acid  contents  from  the  stomach  high  up  in  the 
duodenum. 

In  this  same  paper,  in  which  the  importance  of  bile  in  fat- 
digestion  was  demonstrated,  attention  was  called  to  the  fact  that 
the  presence  of  a  gall-bladder  served  an  important  purpose  in  fat- 
digestion,  in  that  it  supplied  bile  in  large  quantities  and  at  the 
proper  time  to  assist  the  pancreatic  juice  in  splitting  fats.  Ani- 
mals which  take  considerable  fat  in  their  food  should  therefore  be 
provided  with  gall-bladders. 

It  was  further  demonstrated  in  this  same  paper  that  0.25  per 
cent,  of  sodium  carbonate  (the  amount  which  the  succus  enteri- 
cus  is  supposed  to  contain)  would  greatly  retard  the  fat-splitting 
properties  of  pancreatic  juice.  I  therefore  concluded  that  in  ani- 
mals taking  considerable  fat  in  their  food  the  anatomical  condi- 
tions should  be  such  as  to  retard  the  rate  of  passage  of  food-stuffs 
through  the  duodenum,  so  that  the  fats  may  be  exposed  to  the 
action  of  pancreatic  juice  in  the  duodenum  long  enough  for  the 
requisite  amount  of  fat-splitting  to  be  accomplished.  Otherwise 
the  food  would  be  hastened  along  the  intestines  and  into  the 
presence  of  sodium  carbonate,  which  would  retard  fat-splitting 
and  consequently  interfere  with  fat-digestion. 

In  1899  I  published  a  second  paper  in  the  y our  rial  of  Physi- 
ology o\\  "The  Influence  of  Bile,  of  Acids,  and  of  Alkalies  on 
the  Proteolytic  Action  of  Pancreatic  Juice."  In  this  paper  I 
demonstrated  that  rabbits'  bile,  when  added  to  rabbits'  pancre- 
atic juice,  acting  upon  neutral  fibrin,  will  markedly  stimulate  the 
proteolytic  power  of  the  juice  ;  in  most  of  the  experiments  the 
juice  was  able  to  do  one-fourth  more  work  in  proteolysis  by 
reason  of  the  presence  of  the  bile.  From  this  physiological  fact  one 
may  reason  by  analogy  that  the  fresh  bile  of  any  animal  will  in- 
crease the  proteolytic  power  of  the  fresh  pancreatic  juice  of  the  same 
animal.  If  this  reasoning  be  well  founded,  then  one  may  con- 
clude that  the  preliminary  mixing  of  the  bile  and  pancreatic  juice 


B.   K.  RACHFORD.  69 

which  occurs  in  some  animals  serves  an  important  physiological 
purpose  in  proteid  digestion,  and  that  all  animals  taking  a  large 
quantity  of  proteids  in  their  food  should  have  such  an  anatomical 
arrangement  of  their  bile  and  pancreatic  ducts  as  will  provide 
for  the  mixing  of  the  bile  and  pancreatic  juice  either  before  or 
directly  after  they  are  brought  into  contact  with  the  food.  It 
follows  also  that  these  animals  should  be  provided  with  gall- 
bladders, that  the  bile  may  be  supplied  in  proper  quantities  and 
at  the  proper  time  to  satisfy  the  demands  of  the  pancreatic  diges- 
tion of  proteids. 

In  this  same  paper  my  experiments  "  led  me  to  the  conclusions 
that  a  small  quantity  of  combined  hydrochloric  acid,  not  greater 
than  one-half  saturation,  will  but  slightly  diminish  the  proteo- 
lytic action  of  rabbits'  pancreatic  juice,  and  that  when  rabbits' 
bile  is  added  to  these  mixtures  the  retarding  influence  of  the 
hydrochloric  acid  is  not  only  neutralized  but  an  actual  increase  in 
proteolysis  is  attained.'*  If  this  principle  of  proteid  digestion 
holds  good  in  all  anim.als,  then  one  would  expect  to  find  in 
proteid-eating  animals  that  the  bile  and  pancreatic  juice  was 
poured  into  the  duodenum  not  only  through  a  common  opening, 
but  that  this  common  opening  was  near  the  pylorus. 

In  1899  I  published  a  paper  in  the  American  Journal  of 
Physiology  on  ■ "  The  Diastatic  Action  of  Pancreatic  Juice." 
From  the  experiments  recorded  in  this  paper  the  conclusion  was 
drawn  that  bile  plays  a  rather  unimportant  role  in  starch  diges- 
tion. It  is,  in  fact,  not  necessary  to  the  diastatic  action  of  pan- 
creatic juice  when  the  juice  is  acting  in  neutral  or  slightly  alka- 
line solution,  but  the  bile  may  be  of  great  assistance  to  pancreatic 
juice — indeed,  almost  necessary  to  its  full  diastatic  action — when 
the  former  is  acting  in  the  presence  of  free  acid.  It  was  also 
shown  in  this  paper  that  both  albumen  and  bile  would,  when 
combined  with  a  small  amount  of  hydrochloric  acid,  somewhat 
increase  the  diastatic  action  of  pancreatic  juice  over  the  amount 
of  work  it  could  do  in  neutral  solution.  If  these  experiments  may 
be  taken  as  evidence  of  the  unimportance  of  bile  in  the  diastatic 
action  of  pancreatic  juice  in  all  animals,  then  one  may  conclude 
that  no  important  physiological  purpose  would  be  served  by  the 
union  of  the  bile  and  pancreatic  ducts  in  animals  purely  herbiv- 
orous, and  that  there  is  no  apparent  physiological  reason  why 
these  animals  should  be  provided  with  gall-bladders. 


70  PANCREATIC    DIGESTION. 

In  the  above  outline  1  have  briefly  reviewed  a  portion  of  the 
work  which  I  have  done  during  the  past  few  years  on  the  diges- 
tive action,  on  various  food-stuffs,  of  rabbits'  pancreatic  juice 
acting  under  various  conditions,  and  from  these  observations  I 
have  attempted  to  make  out  the  anatomical  conditions  which 
would  best  serve  the  physiological  purposes  of  pancreatic  diges- 
tion in  different  animals.  In  following  out  this  line  cf  reason- 
ing I  have  assumed  that  variations  in  the  structure  of  the  diges- 
tive organs  of  different  animals  had  been  determined  by  the  phy- 
siological laws  of  food  digestion.  1  have  also  assumed,  and  in 
this  assumption  there  may  be  room  for  doubt,  that  the  physio- 
logical laws  of  pancreatic  digestion  are  the  same  in  all  animals. 

The  above  observations,  however,  derive  their  importance  not 
so  much  from  the  arguments  which  they  contain  as  from  the  fact 
that  they  are  to  offer  corroborative  testimony  to  the  physiological 
conclusions  which  will  hereafter  be  drawn  from  anatomical  data. 

With  this  prelude  I  shall  now  attempt  certain  conclusions 
concerning  the  laws  of  food  digestion,  from  a  study  of  the  com- 
parative anatomy  of  the  digestive  organs  of  various  animals.  In 
this  study  I  have  classified  all  animals,  according  to  the  character 
of  their  food,  as  herbivorous,  carnivorous,  or  omnivorous.  It  is 
assumed  that  the  herbivorous  animals  partake  chiefly  of  starch, 
the  carnivorous  and  insectivorous  chiefly  of  proteids  and  fats, 
and  the  omnivorous  of  a  fair  proportion  of  all  these  foods. 

"  In  a  comparative  anatomy  study  of  the  kind  here  attempted, 
the  difficulties  are  many  and  the  liabilities  to  draw  false  conclu- 
sions from  misinterpreted  and  incomplete  anatomical  data  are 
very  great.  While  one  may  assume  without  fear  of  contradiction 
that  the  various  anatomical  arrangements  of  the  bile  and  pancre- 
atic ducts  in  different  species  of  mammals  have  a  definite  physio- 
logical significance,  and  that  for  the  most  part  this  anatomical 
arrangement  has  resulted,  by  natural  selection,  from  the  physio- 
logical laws  controlling  the  digestion  of  food,  yet  even  with  this 
preface  it  is  impossible  for  one  to  estimate  in  an  accurate  way 
the  proportionate  influence  which  the  various  physiological  laws 
may  have  had  in  the  development  of  the  existing  anatomical  con- 
ditions. For  example,  one  cannot  say  that  such  physiological 
conditions  as  the  presence  of  a  gall-bladder  discharging  its  bile 
through  a  duct,  common  to  it  and  the  pancreas,  into  the  duode- 
num in  close  proximity  to  the  pylorus  were  developed  in  the~car- 


B.  K.   RACHFORD.  71 

nivora  exclusively  as  a  result  of  the  physiological  laws  of  fat- 
digestion  ;  nor  can  one  say  that  the  physiological  laws  of  proteid 
digestion  have  exclusively  determined  these  conditions.  At  best 
one  can  only  approximately  estimate,  from  existing  physiological 
facts,  the  proportionate  influence  which  either  of  these  factors 
may  have  had  in  determining  the  various  anatomical  arrange- 
ments of  the  bile  and  pancreatic  ducts  in  mammals. 

"  A  source  of  error,  in  attempting  to  draw  physiological  con- 
clusions from  anatomical  data,  lies  in  the  fact  that  there  are 
always  minor  accessory  anatomical  conditions,  the  physiological 
importance  of  which  it  is  difficult  to  estimate.  For  example,  in 
the  carnivora  and  many  omnivora  I  have  noted  the  following 
anatomical  peculiarities  of  the  duodenum  :  It  has  a  horseshoe 
shape,  its  convexity  looking  downward ;  it  gradually  diminishes 
in  caliber,  being  smallest  at  its  junction  with  the  jejunum;  it  is 
closely  attached  to  the  head  of  a  fleshy  pancreas  and  has  a  short 
mesenteric  attachment,  for  which  reasons  it  is  much  less  movable 
than  is  this  portion  of  the  small  intestine  in  the  herbivora.  These 
anatomical  peculiarities  of  the  duodenum  in  the  carnivora  and  in 
some  omnivora  no  doubt  have  a  great  influence  in  diminishing 
the  rate  of  passage  of  food-stufFs  through  the  duodenum,  and  in 
this  way  they  increase  the  duration  of  the  exposure  of  food  to 
the  combined  action  of  the  pancreatic  juice  and  bile  in  the  duo- 
denum. But  it  is  impossible  to  estimate  what  influence  such 
accessory  anatomical  conditions  as  these  may  have  (by  modifying 
the  influence  of  the  physiological  laws  of  food  digestion)  in  de- 
termining the  anatomical  arrangements  of  the  bile  and  pancreatic 
ducts  in  different  species  of  mammals.  Errors  of  inference  from 
this  cause  must  therefore  remain  in  great  part  uncorrected. 

"Another  liability  to  error,  in  such  a  study  as  this,  results 
from  assuming  that  the  same  organs  in  different  orders  of  mam- 
mals always  do  the  same  kind  of  work.  For  example,  the  stom- 
achs of  the  carnivora  and  of  the  herbivora  are  very  different 
organs,  and  are  capable  of  very  different  kinds  of  physiological 
work.  And  here  again  it  is  not  possible  to  estimate  the  influ- 
ence which  differing  anatomical  conditions,  in  other  portions  of 
the  digestive  tract,  may  have  had  in  modifying  the  influence 
which  the  duodenal  digestion  of  food-stuffs  has  had  in  determin- 
ing the  various  arrangements  of  the  bile  and  pancreatic  ducts  in 
different  mammals. 


V2 


PANCREA  TIC    DIGESTION. 


"  Another  and  most  important  cause  of  error,  in  making  phy- 
siological deductions  from  comparative  anatomy  data,  is  that  the 
primitive  type  from  which  the  animal  is  descended  is  an  influen- 
tial factor  in  determining  structure  in  all  subsequent  generations. 
For  example,  the  seal  and  the  porpoise  are  descended  from  very 
differently  constructed  ancestors,  and  this  fact  no  doubt  accounts 
for  the  presence  of  a  gall-bladder  in  the  seal  and  its  absence  in 
the  porpoise,  notwithstanding  the  fact  that  for  numberless  gen- 
erations both  have  been  purely  fish-eaters." 

Notwithstanding  these  difficulties,  I  shall  attempt  to  make 
physiological  deductions  from  such  comparative  anatomy  data  as 
I  have  been  able  to  collect.  The  following  tables  I  have  taken 
from  a  former  article  of  mine  published  in  this  journal  in  De- 
cember, 189^,  and  due  acknowledgement  is  hereby  made  not 
only  for  these  tables,  but  for  the  above  quotation, 

QUADRUMANA. 


Species  and  Name  of  Animal. 


Man 

Troglodyte  Gorilla 

Chimpanzee  (  Troglodytes  niger).... 

Common  Macaque  Monkey  (Ma- 
ra nis  rviiomolgiis) 

Capuchin  Monkey  (Cel'/is  capnci- 
niis) 

Lemur,  nocturnal  {Indris  brevi- 
raiidattis) 

Lemur,  diurnal  (Lemur  mongoz).... 

Lemur,  ruffed  (Lemur  varius) 


Common  open- 

Gall-duct 

ing  of  bile  and 
pancreatic 

Presence 

of  gall- 

opening 
is  distant 

Food  of 

ducts  is  from 

bladder. 

from 

pylorus: 

pylorus: 

8  cm. 

Yes. 

8  cm. 

Omnivorous. 

25  cm. 

-i'es. 

25  cm. 

Herbivorous. 

15  to  20  cm. 

Yes. 

IS  to  20 cm. 

Herbivorous. 

3  cm. 

Yes. 

3  cm. 

Omnivorous. 

2  cm. 

Yes. 

2  cm. 

Insectivorous. 

3  cm. 

Yes. 

3  cm. 

Insect,  chiefly. 

734  cm. 

Yes. 

734  cm. 
1I4  cm. 

Omnivorous. 

jl^  cm. 

Yes. 

Insect,  chiefly. 

This  table  contains  three  insectivorous  animals,  namely,  the 
Capuchin  monkey,  the  nocturnal  lemur,  and  the  ruflfed  lemur. 
It  will  be  observed  that  in  these  animals  the  common  openings 
of  the  bile  and  pancreatic  ducts  are  placed  very  near  the  pylorus. 
If  this  location  of  the  common  duct  be  compared  with  its  location 
in  the  herbivorous  gorilla  and  chimpanzee,  which  belong  to  this 
same  species,  the  contrast  is  very  striking.  In  the  gorilla  the 
common  duct  is  located  twenty-five  centimetres  from  the  pylorus, 
and  in  the  ruffed  lemur  it  approaches  as  near  as  one  and  a  fourth 
centimetres.  If  one  assumes  that  the  anatomical  conditions  as 
they  occur  in  these  animals  serve  the  best  purposes  of  food  diges- 
tion, then  one  must  infer  that  this  anatomical  arrangement  which 
gives  to  insectivorous  animals  a  common  opening   for  their  bile 


B.   K.   RACHFORD.  73 

and  pancreatic  ducts  and  places  this  common  opening  near  the 
pylorus  serves  an  important  physiological  purpose  in  the  diges- 
tion of  fats  and  proteids — the  chief  food-stuffs  of  these  animals. 
From  these  facts  one  may  infer  that  the  preliminary  mixing  of 
bile  and  pancreatic  juice  before  they  enter  the  duodenum  is  of 
physiological  importance  in  the  digestion  of  fats  and  proteids, 
and  this  inference  will  be  strengthened  into  a  conclusion  by  a 
study  of  subsequent  tables.  From  this  table  one  may  also  infer 
that  this  preliminary  mixing  of  bile  and  pancreatic  juice  is  of 
importance  in  the  digestion  of  starchy  foods,  since  both  the 
herbivorous  chimpanzee  and  gorilla  have  a  common  opening  for 
the  bile  and  pancreatic  ducts  ;  but  a  study  of  subsequent  tables 
will  show  that  this  inference  is  fallacious.  An  important  phy- 
siological inference,  however,  which  may  be  made  from  the 
above  table  is  that  the  pancreatic  digestion  of  fats  and  proteids 
as  it  occurs  in  insectivora  is  facilitated  by  bringing  the  bile  and 
pancreatic  juice  in  contact  with  the  food  very  soon  after  it  leaves 
the  stomach,  and  that  the  pancreatic  digestion  of  starches  as  it 
occurs  in  herbivora  is  not  facilitated  by  bringing  these  juices  in 
contact  with  the  food  high  up  in  the  duodenum.  If  one  remem- 
bers that  the  duodenal  contents,  in  the  carnivora,  are  acid,  and 
that  the  food  as  it  leaves  the  stomach  contains  more  or  less  com- 
bined hydrochloric  acid,  one  is  led  to  the  inference  that  the  pan- 
creatic digestion  of  fats  and  proteids  is  facilitated  in  the  insec- 
tivora not  only  by  the  bile,  but  also  by  such  acids  as  may  be 
combined  with  the  food-stuffs  as  they  enter  the  duodenum.  If 
these  inferences  be  not  true,  then  no  apparent  physiological  pur- 
pose is  served  by  placing  the  common  bile  and  pancreatic  ducts 
near  the  pylorus  in  the  Capuchin  monkey,  nocturnal  lemur,  and 
ruffed  lemur,  the  three  insectivora  in  the  above  table. 

These  inferences  concerning  the  laws  which  gove'rn  the  diges- 
tion of  fats  and  proteids  in  the  insectivora  are  of  more  value  as 
they  are  compared  with  the  inferences  made  from  the  same  table 
concerning  the  pancreatic  digestion  of  starches  in  the  herbivor- 
ous chimpanzee  and  gorilla.  If  one  may  assume  that  starch 
digestion  in  these  animals  is  facilitated  by  the  anatomical  arrange- 
ment which  pours  the  bile  and  pancreatic  juice  into  the  duodenum 
twenty  to  twenty-five  centimetres  below  the  pylorus  (since  the 
lower  portion  of  the  duodenum  is  alkaline  in  the  herbivora),  then 
will  follow  the  inference  that  pancreatic  juice  assisted  by  the  bile 


74 


PANCREATIC    DICESTION. 


can  do  its  best  diastatic  work  in  a  feebly  alkaline  medium.  If,  on 
the  other  hand,  an  acid  medium  is  much  more  favorable  to  the 
diastatic  action  of  pancreatic  juice  than  an  alkaline,  then  would 
the  bile  and  pancreatic  ducts  be  placed  in  the  herbivora,  as  they 
are  in  the  carnivora,  high  up  in  the  duodenum  near  the  pylorus. 
The  inference  therefore  seems  plain  that  an  acid  medium  has  no 
advantages  over  an  alkaline  medium  in  the  pancreatic  digestion 
of  starches.  That  the  pancreatic  juice  prefers  an  alkaline  medium 
for  the  digestion  of  starches  is  also  indicated  by  the  fact,  above 
referred  to,  that  in  the  herbivora  the  intestinal  contents  lose 
their  acidity  sooner  and  become  more  alkaline  than  in  the  car- 
nivora, and  also  by  the  fact  that  the  bile  of  herbivorous  animals 
has  a  greater  degree  of  alkalinity  than  the  bile  of  the  carnivora. 
If  one  again  refers  to  the  table  it  will  be  seen  that  the  omniv- 
orous animals  of  this  species,  viz.,  man  and  the  diurnal  lemur, 
have  the  common  opening  of  their  bile  and  pancreatic  ducts  not 
so  near  the  pylorus  as  the  carnivora  nor  so  far  away  as  the  her- 
bivora, which  would  indicate  that  nature  had  compromised  on 
this  mid-distance  as  between  the  extremes  demanded  by  the  laws 
of  food  digestion  in  the  purely  carnivorous  and  herbivorous 
animals. 

CHEIROPTERA. 


Species  and  Name  of  Animal. 


Fruit  Bat  (Pteio/^iis  Edvjardsii). 
Insect  Bat  (  VespertiLio  noctula). 


Common  open- 
ingof  bile  and 

pancreatic 

ducts  is  from 

pylorus: 


T.i\4^  cm. 
3^  cm. 


Presence 
of  Rail- 
bladder. 


Yes. 
Yes. 


Gall-duct 
opening 

is  distant 

from 
pylorus: 


:^cm. 
\  cm. 


Food  of 
animal. 


Herbivorous. 
Insectivorous. 


This  table  is  here  inserted  in  support  of  the  above  inferences 
drawn  from  the  Quadrumana.  The  contrast  is  very  striking 
between  the  "location  of  the  openings  of  the  common  bile  and 
pancreatic  ducts  in  the  fruit-eating  and  insect-eating  bat.  The 
insectivorous  bat,  which  takes  a  large  quantity  of  fats  and  pro- 
teids  in  its  food,  has  the  common  opening  of  bile  and  pancreatic 
ducts  immediately  below  the  pylorus,  where  these  juices  may 
come  in  contact  with  the  acid  food-stuffs  as  they  leave  the  stom- 
ach ;  while  in  the  fruit  bat  this  opening  is  twelve  and  one-half 
centimetres  from  the  pylorus.  The  marked  difference  that  here 
exists  in  the  location  of  these  ducts  emphasizes  the  great  advan- 
tage  in    food   digestion   which   must   accrue   to    the   carnivorous 


B.   K.  RACHFORD. 


75 


animals  in  having  the  common  opening  of  the  bile  and  pancreatic 
ducts  in  close  proximity  to  the  pylorus,  and  it  also  emphasizes 
the  fact,  above  noted,  that  this  anatomical  arrangement  is  of  no 
physiological  advantage  to  herbivorous  animals,  otherwise  the 
bile  and  pancreatic  juice  would  enter  the  duodenum  of  the  fruit 
bat,  as  it  does  in  the  insect  bat,  near  the  pylorus,  instead  of 
twelve  and  a  half  centimetres  below. 


CARNIVORA. 


Species  and  Name  of  Animal. 


I.ion  (/■>//.«  leo) 

Tiger  (  Felis;  ligris) 

I^eopard  (Felis  Leopardus) 

Domestic  Cat  (Felis  domesiica) 

Wildcat  {Fell's  Lynx  riifiis) 

Lynx  (  Fell's  Lynx  canadensis) 

Panther  {Felis  concolor) 

Coyote,  American  {Cam's  latrans) 
Wolf  (Canis  lupus) 

Fox,  African  ( Cam's  Vulpes  iiilo- 
ticus\ 

Fox,  European  ( Canis  Vulpes  viil- 
garis\ 

Dog,  Japanese  ( Canis  Nyctereutes 
procyonides) 

Dog,  domestic  (Canis  fainiliaris) 

Skunk  I Mef<l/itis  mephitica) 

Badger  {Meles  vulgaris) 

Brown  Bear  (Ursus  arcius) 

Raccoon,  Albino  {Ursus  Protyon 
lotor) ." 

Coati,  Mexican  (Ursus  Nasua 
narica) 

Hedgehog  (Insectivora  Erinaceus 
europteus) 


Common  opening 
of  bile  and  pan- 
creatic  ducts  is 
from  pylorus: 

Q 

15 

bo 
0 

n 

Oh 

tic- 
c  e 
•-  0 

11  = 
■?^  £ 
—  „  >^ 

0 

E 

c 
t« 

0 

0 

6  cm. 
5  cm. 
4  cm. 
2I2  cm. 
3  cm. 
Near. 
Near. 

Yes. 
Yes. 
Yes. 
Yes. 
Yes. 
Yes. 
Yes. 
Yes. 
Yes. 

Yes. 

Yes. 

Yes. 
Yes. 

Yes. 
Yes. 

Yes. 

Yes. 
Yes. 
Yes. 

6  cm. 
5  cm. 

4  cm. 
2J/2  cm. 
3  cm. 
Near. 
Near. 
2.6  cm. 
Near. 

i^cm. 
Near. 

3  cm. 

5  cm. 

23.2  cm. 

Carnivorous. 

Carnivorous. 

Carnivorous. 

Carnivorous. 

Carnivorous. 

Carnivorous. 

Carnivorous. 

3.8  cm. 
On     same 
level. 

5I.J  cm. 

ji^cm. 

5*2  cm. 
Acces.  pan. 
duct, from 
pyl.7.5cm. 

Carnivorous. 

Near. 

Carnivorous. 
Omnivorous. 

Omnivorous. 

Omnivorous. 

S  cm. 
2j^  cm. 

Omnivorous. 
Carn.  chiefly. 

2  cm. 

Above  bile 
duct. 

Omnivorous. 

Acces.  pan. 
duct. 

4  cm. 

3  cm. 

2  cm. 

Omnivorous. 

4  cm. 
3  cm. 
2  cm. 

Omnivorous. 

Insectiv.  etc. 

Insectivorous. 

It  will  be  noted  that  twelve  of  the  nineteen  animals  in  the 
above  table  are  carnivorous,  and  that  in  all  of  these  carnivorous 
animals,  excepting  the  American  coyote,  the  bile  and  pancreatic 
juice  are  poured  into  the  duodenum  in  close  proximity  to  the 
pylorus  either  through  a  common  opening  or  through  separate 
openings  entering  the  duodenum  on  the  same  level,  thus  provid- 
ing for  the  mixing  of  the  bile  and  pancreatic  juice  immediately 
they  are  poured  into  the  duodenum.  Even  in  the  American 
coyote  the  distance — three  and  one-half  centimetres — between 
the  openings  of  the  bile  and   pancreatic    ducts  is  so  short  that  it 


76  PANCREATIC    DIGESTION. 

may  liardly  be  considered  as  an  exception  to  the  rule  that  car- 
nivorous animals  have  an  anatomical  arrangement  which  provides 
for  the  mixing  of  bile  and  pancreatic  juice  before,  or  directly 
after,  their  entrance  into  the  intestine.  It  is  interesting  to  note 
in  this  table  that  in  the  large  animals  like  the  lion,  the  tiger,  and 
the  leopard,  which  are  exclusively  carnivorous,  the  common  bile 
and  pancreatic  duct  approaches  so  closely  to  the  pylorus  (from 
four  to  six  centimetres)  that  one  must  believe  there  is  decided 
physiological  advantage  in  this  arrangement  which  provides  that 
the  bile  and  pancreatic  juice  shall  come  in  contact  with  acid  food- 
stuffs immediately  after  they  are  discharged  from  the  stomach. 
It  appears,  in  fact,  from  a  study  of  the  comparative  anatomy  of 
the  bile  and  pancreatic  ducts  in  all  the  herbivorous,  omnivorous, 
and  carnivorous  animals  in  the  tables  here  presented  that  one  may 
formulate  the  rule  that  the  more  strictly  carnivorous  the  animal^ 
the  ?)iore  closely  will  the  opening  of  the  conunon  bile  and  pancre- 
atic duct  approach  the  pylorus.  These  facts  surely  justify  us  in 
concluding  that  the  pancreatic  digestion  of  fats  and  proteids  is 
facilitated  by  the  presence  of  bile  and  combined  acids  to  the 
extent  that  they  exist  in  food-stuffs  high  up  in  the  duodenum,  and 
warrant  us  in  concluding  that  the  fundamental  principles  which 
govern  fat  and  proteid  digestion  in  the  carnivora  are  the  same 
as  in  the  rabbit,  since,  as  noted  in  the  preface,  laboratory  experi- 
ments with  the  bile  and  pancreatic  juice  of  this  latter  animal  lead 
to  the  same  physiological  conclusions. 

In  the  above  table,  however,  special  interest  attaches  to  a 
study  of  the  arrangement  of  the  bile  and  pancreatic  ducts  in  the 
seven  omnivorous  animals.  Here  one  finds  that  the  African  fox, 
the  European  fox,  the  Japanese  dog,  and  the  badger  have  sepa- 
rate openings  for  their  bile  and  pancreatic  ducts.  In  the  first 
three  the  pancreatic  juice  is  poured  into  the  duodenum  five  and 
one-half  centimetres  below  the  opening  of  the  bile  duct.  In  the 
other  three  omnivorous  animals  in  this  table,  namely,  the  domes- 
tic dog,  the  brown  bear  and  the  raccoon,  one  finds  in  two  of 
these  animals  an  accessory  pancreatic  duct  opening  below  the 
common  duct;  and  in  only  one,  the  raccoon,  do  we  find  all  of 
the  bile  and  pancreatic  juice  poured  through  a  common  opening 
into  the  duodenum  in  close  proximity  to  the  pylorus.  It  is  quite 
evident,  therefore,  from  a  study  of  this  table  that  in  omnivorous 
animals  there  is  less  physiological  necessity  than  in  the  carnivora 


B.   K.  RACHFORD. 


77 


for  the  preliminary  mixing  of  the  bile  and  pancreatic  juice  before 
they  come  in  contact  with  food-stuffs.  The  physiological  im- 
portance of  this  variation  will  appear  in  the  following  table  : 


PACHYDERM ATA. 


Species  and  Name  of  Animal. 

Common  openinj^: 
of  bile  and  pan- 
creatic  ducts  is 
from  pylorus: 

5  e 
"  5  •■ 

rt  «  ? 

bi; 
0 

li 

a, 

.E  0 

3  «  5 

rJ.-  G. 

0 

■A 

0 

5 
0 

Horse  (Equus  cabal  I  us) 

ij  cm. 
15  cm. 
lb  cm. 

No. 
No. 
No. 

No. 

Yes. 

No. 
No. 

IS  cm. 
15  cm. 
10  cm. 

Herbivorous. 

Ass  {  Ei/iitis  iisiittis) 

Herbivorous. 

Elephant  {Elefhas  iiidi'ni.t).... 
Tapir  (  Tti/'iiiis  amt-ri'( amis)  .. 

Pig  (Siis /ami ! ian's) 

Accessory  duct 
S  cm.  lower. 

Same  level, 
common 
openinar. 

10  to  20  cm. 

Same  level. 
One  2  cm. 
lower. 

Herbivorous. 
Herbivorous. 

2  to  5  cm. 

15  cm. 
2.5  cm. 

Omnivorous. 

Rhinoceros    (Rhinoceros    uni- 
cornis)               .    .                 

15  cm. 
2.5  cm. 

Herbivorous. 

Hyrax  {Hyrax  capensis) 

In  this  table  we  have  emphasized  the  unimportance  of  the 
gall-bladder  in  herbivorous  animals.  The  omnivorous  pig  is  the 
only  animal  in  the  table  provided  with  a  gall-bladder.  In  all  of 
the  six  herbivorous  animals  it  is  absent.  The  absence  of  the 
gall-bladder  in  these  herbivorous  animals  clearly  indicates  the 
unimportance  of  this  organ  in  starch  digestion.  The  presence  of 
a  gall-bladder  in  all  carnivorous  animals  indicates  that  there  is  a 
physiological  necessity  for  a  reservoir  of  this  -kind  for  holding 
the  bile  so  that  it  can  be  discharged  in  quantity  into  the  duode- 
num during  the  pancreatic  digestion  of  fats  and  proteids.  That 
this  reservoir  for  bile  is  unnecessary  in  herbivorous  or  starch- 
eating  animals  is  clearly  proven  by  the  fact  that  it  gradually 
diminishes  in  size  as  the  animal  takes  less  fat  and  proteid  in  its 
food,  till  in  some  of  the  exclusively  herbivorous  animals,  as  noted 
in  the  above  table,  it  is  absent.  Clearly,  then,  the  character  of 
the  food  in  different  species  of  animals  determines  the  presence 
and  size  of  the  gall-bladder.  In  the  carnivora  the  gall-bladder 
is  large,  and  in  the  herbivora  it  is  small  or  altogether  absent, 
while  in  the  omnivora  it  is  intermediate  in  size.  The  physiologi- 
cal inference  from  these  facts  is  that  bile  does  not  serve  any  very 
important  purpose  in  the  pancreatic  digestion  of  starches,  for 
certainly  nothing  short  of  the  unimportance  of  bile   in  the  pan- 


78  PANCREATIC    DIGESTION. 

creatic  digestion  of  starches  would  account  for  the  gradual 
diminution  in  size  and  final  loss  of  the  gall-bladder  and  a  conse- 
quent inability  to  regulate  the  flow  of  bile  according  to  the  needs 
of  pancreatic  digestion  in  animals  as  they  become  more  and  more 
exclusively  herbivorous.  This  physiological  inference  corrects 
the  physiological  inference  made  from  the  Qjiiadrumana,  that 
"bile  is  of  importance  in  the  pancreatic  digestion  of  starches." 
Evidently  this  inference  was  made  from  incomplete  anatomical 
data.  The  inference,  however,  just  drawn  from  the  above  table, 
that  bile  is  of  little  value  to  pancreatic  juice  in  the  digestion  of 
starches,  is  made  stronger  by  a  study  of  subsequent  tables,  and  is, 
moreover,  in  accord  with  the  physiological  conclusion,  drawn  from 
laboratory  experimentation,  and  outlined  in  the  preface  to  this 
paper,  that  "  bile  has  Little  if  any  favorable  action  on  the  diastatic 
action  of  pancreatic  juice." 

In  the  study  of  the  above  table  it  will  be  noticed  that  there  is 
a  tendency  to  the  separation  of  the  bile  and  pancreatic  ducts  in 
herbivorous  animals.  In  many  of  these  animals  the  opening  of 
the  pancreatic  duct  is  some  distance  below  the  bile  duct.  This 
is  a  fact  in  comparative  anatomy  of  no  little  importance.  This 
separation  of  bile  and  pancreatic  ducts  as  noted  in  the  last  table 
occasionally  occurs  in  the  omnivora,  but  it  never  occurs  in  the 
carnivora.  In  these  last  named  animals  the  bile  and  pancreatic 
ducts  enter  the  duodenum  by  a  common  opening,  except  in  a  few 
instances  where  they  enter  on  a  common  level,  thus  providing 
for  the  mixing  of  bile  and  pancreatic  juice  before  or  directly 
after  they  enter  the  duodenum.  These  facts  clearly  indicate  that 
the  preliminary  mixing  of  bile  and  pancreatic  juice  is  unimport- 
ant in  the  herbivora.  It  is  also  clear  from  a  study  of  all  the 
tables  here  presented  that  the  union  or  separation  of  the  bile  and 
pancreatic  ducts,  as  well  as  the  location  of  the  openings  of  these 
ducts,  with  reference  to  the  pylorus,  have  been  determined  in 
different  animals  by  the  character  of  their  food-stuffs.  The  car- 
nivora have  a  common  opening  near  the  pylorus.  The  herbivora 
either  have  a  common  opening  far  from  the  pylorus,  or  the  ducts 
are  separated  and  the  pancreatic  opening  is  far  from  the  pylorus, 
while  the  gall  duct  may  remain  near  the  pylorus.  The  omnivora 
present  an  anatomical  arrangement  of  these  ducts  which  is  a 
compromise  between  the  extremes  as  found  in  the  carnivora  and 
herbivora.      From  these  facts  the  physiological   inference  may  be 


B.   K.  RACHFORD.  79 

drawn  tlnit  bile  is  not  necessary  to  the  pancreatic  digestion  of 
starches.  This  inference  accords  with  that  above  drawn  from 
the  comparative  anatomy  of  the  gall-bladder  in  these  animals,  as 
well  as  that  drawn  from  chemical  experiments  made  with  rabbits' 
bile  and  pancreatic  juice  as  outlined  in  the  preface. 


MARSUPIALIA. 


Species  and  Name  of  Animal. 

Common  open- 
ing of  bile  and 

pancreatic 

ducts  is  from 

pylorus: 

Presence 
of  gall- 
bladder. 

Gall-duct 
opening 

is  distant 

from 
pylorus: 

Food  of 
animal. 

Dasyure  ( Dasymus  virierriuus),. 
Opossum  {Dfdelphys  virgiiiiaiia) 

Bandicoot  (Perameles  iiahila) 

Kangaroo  (Macropus  gigauteus).. 

2.5  cm. 
2.5  cm. 
2.5  cm. 
15  to  25  cm. 

Yes. 
Yes. 
Yes. 
Yes. 

2.5  cm. 
2.5  cm. 
2.5  cm. 
15  to  25  cm. 

Carn.A-  insect. 
Carn.&  insect. 
Insect.  &  herb. 
Herbivorous. 

In  this  table  we  have  three  insectivorous  animals  and  one 
herbivorous,  and  the  contrast'  in  the  arrangement  of  the  bile  and 
pancreatic  ducts  in  these  animals  is  even  more  striking  than  in 
the  previous  tables.  The  insectivorous  dasyure,  opossum  and 
bandicoot  have  the  common  opening  of  their  bile  and  pancreatic 
ducts  within  two  and  one-half  centimetres  of  the  pylorus, 
while  the  herbivoro.us  kangaroo  has  the  common  opening  of  these 
ducts  from  fifteen  to  twenty-five  centimetres  below  the  pylorus. 
Here  again  we  have  emphasized  the  physiological  necessity  in 
the  carnivora  of  mixing  the  bile  and  pancreatic  juice  high  up  in 
the  duodenum,  and  the  physiological  importance  in  the  herbivora 
of  removing  the  pancreatic  duct  some  distance  from  the  pylorus. 

PINNIPEDIA. 


Species  and  Name  of  Animal. 

Common  open- 
ing of  bile  and 

pancreatic 

ducts  is  from 

pylorus: 

Presence 
of  gall- 
bladder. 

Gall-duct 
opening 

is  distant 

from 
pylorus: 

Food  of 
animal. 

Seal  (Plioca  vilttlina) 

Sea  Bear  {Otari'a  tirsina) 

6.5  cm. 
5  cm. 

Yes. 
Yes. 

6.S  cm. 
Scm. 

Carnivorous. 
Carnivorous. 

In  the  two  carnivorous  animals  of  this  species  we  have  the 
same  arrangement  of  the  bile  and  pancreatic  ducts  which  we 
have  noted  in  the  carnivorous  animals  in  the  previous  tables,  and 
the  same  inferences  may  be  drawn. 

In  the  two  herbivorous  animals  next  presented  one  notes,  in 
the  small  gall-bladders,  an  effort  to  get  rid  of  this  organ,  which 
is  of  little  use  in  herbivorous  animals,  and   in   the  location  of  the 


8o 


PANCREATIC    DK.ESTIOX. 


SIRENIA. 


Species  and  Name  of  Animal. 

Distance 

between  bile 

and 

panereatic 

ducts. 

Presence 

ofirall- 

bhidder. 

Gall-duct 
openintt 

is  distant 

from 
pylorus: 

Food  of 
animal. 

Manatee  {ManatKs  Ititirostn's) 

Same  level. 
Same  level. 

Yes. 
Yes. 

13  cm. 
12  cm. 

Herbivorous. 
Herbivorous. 

pancreatic  duct  some  distance  from   the  pylorus   one   notes  the 
arrangement  commonly  found  in  herbivora. 


HODENTIA. 


Sfii.2 

C  i 

_!, 

."  rt  „  " 

j! 

=  Cii  i 

>  ^i£ 

i«) 

S"- 

;; 

Species  and  Name  of  Animal. 

■"—  = 

0 

0  c  .. 

1 

S"£^  S 

c     -S 

5-^ 

^   —  *- 

0 
-a 

0 

^00^*- 

.—  —  \i 

£.Q 

0 

'J 

Q 

0^ 

0 

Rabbit  (LapKs  riiitir/i/iis) 

30  to  40  em. 

Yes 

(small). 

i;-4cm. 

Herbivorous. 

Rat  {Mils  drfiimauiis) 

2.5  cm. 

No. 

2.5  cm. 

Omnivorous. 

Beaver  ( Castor  fiber) 

4fS  t-m. 
S^.-i  cm. 

Yes. 

Yes. 

7-Scm. 
I  cm. 

Herbivorous. 

Porcupine  ( S/>iii^iiriis prehensilis') 

Herbivorous. 

The  omnivorous  rat  has  no  gall-bladder.  This,  from  the  point 
of  view  presented  in  this  paper,  is  a  decided  disadvantage  in  the 
pancreatic  digestion  of  fats  and  proteids.  This  disadvantage, 
however,  is  offset  in  the  rat  by  an  anatomical  arrangement  which 
pours  the  bile  and  pancreatic  juice  through  a  common  opening  in 
very  close  proximity  to  the  pylorus.  The  rabbit,  the  beaver  and 
the  porcupine,  on  the  other  hand,  all  have  gall-bladders,  which, 
from  the  argument  presented  in  this  paper,  they  have  little  use 
for.  The  gall-bladders  of  these  animals,  however,  are  small,  and 
will  perhaps  in  time  be  altogether  lost.  The  beaver  and  the  rab- 
bit, however,  emphasize  the  apparent  physiological  importance 
to  the  herbivora  of  removing  the  opening  of  the  pancreatic  duct 
far  from  the  pylorus.  The  beaver  has  tlie  distinction  of  having 
the  distance  between  the  openings  of  its  bile  and  pancreatic 
ducts  greater  than  that  of  any  other  animal  noted  in  these  tables ; 
and  the  rabbit,  with  the  opening  of  its  pancreatic  duct  from  thirty 
to  forty  centimetres  below  the  opening  of  the  bile  duct,  enjoys 
the  distinction  of  being  in  this  regard  second  only  to  the  beaver. 
From  these  facts  it  appears  that  while  the  physiological  laws  of 
food  digestion  in  herbivorous  animals  may  demand  that  the  pan- 


B.   K.  RACHFORD. 


8i 


creatic  juice  be  poured  into  the  duodenum  some  distance  below 
the  pylorus,  this  demand  does  not  carry  with  it  the  necessity  that 
the  bile  duct  should  enter  at  this  same  low  level.  The  fact,  how- 
ever, that  in  many  herbivora  the  bile  and  pancreatic  juice  are 
poured  through  a  common  opening  into  the  duodenum  proves 
that  bile,  while  it  may  not  increase,  certainly  does  not  retard  the 
diastatic  action  of  pancreatic  juice  ;  this  physiological  inference 
is  in  accord  with  that  drawn  from  laboratory  study  of  the  dias- 
tatic action  of  rabbits'  pancreatic  juice  as  outlined  in  the  preface 
to  this  paper. 

KUMIXAXTIA. 


Species  and  Name  of 
Animal. 

Ccimnion  opening 
of  bile  and  pan- 
creatic ducts   is 
from  pylorus : 

Distance  between 
bile     and     pan- 
creatic ducts. 

Presence  of  gall- 
bladder. 

Gall-duct  opening 
is   distant   from 
pylorus : 

0 

s 

c 

Ox  (  Bos  taurtix^ 

35  to  50  cm. 

Yes. 
Yes. 

Yes. 
Yes. 

No(2toi'). 

No. 

No. 

25  to  30  cm. 
301040  cm. 

12.2  cm. 
30  to  40  cm. 

2.;  cm. 

58  cm. 

28  cm . 

GoAt  (Co /'ro  lihcHs) 

30  to  40  cm. 

12.2  cm. 
30  to  40  cm. 

25  cm. 

58  cm. 

28  cm . 

Herbivorous. 

Pygmy  Deer,  Malay  (  Tni- 
•^11 /lis  Stanles^anus) 

Sheep  (  Ovis  dries) 

Herbivorous. 

Girart'e       (Camelopardalis 

Gii-affo) 

Herbivorous. 

Camel     ( Cameliis     hactri- 
iDiris) 

Herbivorous. 

Dromedary  ( Camelus  dro- 
medarius) 

Herbivorous. 

In  this  table  we  have  seven  herbivorous  animals,  all  of  whom 
have  the  opening  of  their  pancreatic  ducts  far  below  their  py- 
lorus. In  all  of  these  animals  the  primitive  type  has  maintained 
the  union  between  the  bile  and  pancreatic  ducts,  and  placed  them 
together  many  centimetres  below  the  pylorus.  In  the  ox,  how- 
ever, this  union  of  the  bile  and  pancreatic  ducts  is  lost,  and  the 
opening  of  the  pancreatic  duct  is  carried  far  below  that  of  the 
bile  duct  and  the  pylorus.  These  facts  offer  corroborative  testi- 
mony to  the  physiological  conclusions  drawn  from  the  study  of 
the  herbivorous  animals  in  the  preceding  tables.  The  uselessness 
of  the  gall-bladder  to  herbivora  is  here  again  emphasized  by  its 
absence  in  the  giraffe,  camel  and  dromedary,  for  surely  the  dis- 
appearance of  an  organ  is  proof  sufficient  that  it  served  no  im- 
portant physiological  purpose.  In  the  camel  the  gall-bladder  is 
still  occasionally  found.  In  three  dissections  made  by  Dr.  J.  H, 
S.  Jackson  it  was  absent  in  two  and  present  in  one, 


82 


PANCREATIC    DIGESTION. 


EDENTATA. 


Species  iiiid  Nniiie  of  AniiiKil. 

Common  open- 
ing-of  bile  and 

pancreatic 

ducts  is  from 

pylorus: 

Presence 

of  gall- 
bladder. 

Gall-duct 
opening: 

is  distant 

from 
pylorus: 

Food  of 
animal. 

Armadillo  (  Dasypus  i^igas) 

Small   Ant-eater    { XtvrmiTofhaaa 

Jidiirtvli(s) ". ',  ... 

Scm. 
1-^4  cm. 

5  <■'"'• 
2  cm. 

Yes. 
Yes. 
Yes. 
Yes. 

No. 
Small. 

5  cm. 
r'4  cm. 
5  c"'- 
2  cm . 
10  cm. 
2.5  cm. 

Omnivorous. 

Taniandura  Ant-eater  i  Myrmeco- 
l'lnii;a  tiiiiiaiidiin's)         

Cape   Ant-eater  (Orycteropiis  ra- 

p'lisis) '„ 

Two-toed  Sloth  {C'//(>/a-/>ns  didac- 

/y/i/s)     

Herbivorous. 

Three-toed  Sloth   (  /inidypus   Iri- 
dactvlus)  

In  this  table  we  have  two  herbivorous  animals — one,  the  two- 
toed  sloth,  has  no  gall-bladder,  and  the  other,  the  three-toed  sloth, 
has  a  small  gall-bladder.  This  is  in  contrast  with  the  insectivor- 
ous and  omnivorous  animals  of  this  species,  all  of  which  have 
gall-bladders.  It  appears,  therefore,  not  only  from  this  table, 
but  from  all  previous  tables,  that  the  gall-bladder  is  disappearing 
in  herbivorous  animals,  and  that  the  influence  of  the  primitive 
type  is  in  great  part  responsible  for  the  presence  of  the  gall- 
bladder in  these  animals. 


M  0  N  O  r  R  E  M  A  T  A . 


Species  and  Name  of 
Animal. 

Common  opening 

of  bile  and 

pancreatic  ducts  is 

from  pylorus: 

Presence 

of  gall- 
bladder. 

Gall-duct 
opening 

is  distant 

from 
pylorus: 

Food  of 
animal. 

Duckbill     (  Ornitliorliyncliux 
paradoxus ) ' 

2  cm. 

3  cm.  or  same  level. 

Large. 
Large. 

2  cm. 
2  cm. 

Insectivorous, 

Australian  Hedgehog- ( £r//- 

idna  h  ysln'x ) 

The  large  gall-bladders  and  common  openings  of  the  bile  and 
pancreatic  ducts  near  the  pylorus  in  these  animals  support  the 
conclusions  previously  drawn  from  the  study  of  the  carnivora  in 
the  preceding  tables. 

In  the  following  table  we  have  presented  three  carnivorous 
animals,  in  all  of  which  the  gall-bladder  is  absent.  This  is  a 
most  important  exception,  since  the  animals  of  this  species  are 
the  only  carnivorous  animals  (presented  in  these  tables)  not 
having  gall-bladders.  The  absence  of  the  gall-bladder  in  these 
animals  is  no  doubt  a  disadvantage  to  them  in  food  digestion  ; 
but   nature  apparently  attempts  to  right  this  defect  by  giving  to 


B.   K.  R AC H FORD.  S3 

CETACEA. 


Common  opening       t,  t    /-^    h  j      .. 

Species  and  Name  of  bile  and     ^        Presence  !    Gall-dnct  opening  Food  of 

"    of  Animal.  panc^reatic^duc-ts  is       ^^l;  ^^  ^^^r  -"-'■ 


Whale      \Pliyseter  j 

macrocfphaltif)...     Immediately  below. i  No.  Immediately  below.    Carnivorous. 

Dolphin     {Dflplii- 

HKs  dt-l/^liis\  Immediately  below.    No.  Imniediatelv  below.    Carnivorou.'s. 

Porpoise  (  P/iocteiiu 

10  lit  munis) I  Immediately  below.   No.  Immediately  below.    Carnivorous. 


these  animals  a  common  bile  and  pancreatic  duct  opening  imme- 
diately below  the  pylorus.  The  absence  of  gall-bladders  in 
whales  is  therefore  an  exception  which  proves  the  rules  that  the 
physiological  laws  of  food  digestion  in  the  carnivora  demand, 
first,  that  they  shall  have  a  gall-bladder ;  secondly,  that  they 
shall  have  a  common  opening  for  the  bile  and  pancreatic  ducts  ; 
thirdly,  that  this  common  opening  of  the  bile  and  pancreatic 
ducts  shall  be  placed  high  up  in  the  duodenum  close  to  the 
pylorus,  to  provide  for  the  mixing  of  these  juices  with  the  food- 
stuffs soon  after  they  are  discharged  from  the  stomach. 

In  the  whales,  however,  the  physiological  laws  of  food  diges- 
tion have  failed  to  overcome  the  influence  of  the  primitive  type 
in  determining  structure,  and  have  not  for  this  reason  been  able 
to  develop  gall-bladders.  These  laws,  however,  failing  in  this 
particular  have  placed  the  common  opening  of  the  bile  and  pan- 
creatic ducts  in  these  animals  almost  immediately  below  the  py- 
lorus :  in  this  arrangement  apparently  making  an  effort  to  over- 
come the  disadvantages  from  which  these  animals  suffer  by  reason 
of  the  absence  of  gall-bladders. 

In  conclusion  I  desire  to  call  attention  to  certain  important 
facts  in  the  comparative  anatomy  of  the  small  intestine  which  do 
not  appear  in  the  above  tables,  and  yet  are  of  considerable  phy- 
siological importance  to  the  discussion  of  the  questions  considered 
in  this  paper.  These  facts  relate  to  the  influence  whicli  the 
shape  and  mobility  of  the  duodenum  may  have  on  the  rate  of 
passage  of  food-stuffs  along  this  portion  of  the  alimentary  canal. 
They  are  as  fojlows  : 

The  duodenum  in  the  carnivora  is  more  closely  attached  to 
the  head  of  a  fleshy  pancreas  and  has  a  shorter  mesenteric  attach- 
ment than  it  has  in  the  herbivora.  These  facts  make  peristaltic 
and  other  movements  less  iictjye  jn  the  duodenum  of  the  carniv- 


84  PANCREATTC    DIGESTION. 

ora  than  in  the  herbivora,  and  therefore  cause  the  food  to  remain 
longer  in  the  duodenum  of  the  carnivora  than  in  the  herbivora. 
The  horseshoe  shape  of  the  duodenum  in  the  carnivora  may  also 
contribute  to  this  same  end.  It  appears,  therefore,  that  certain 
anatomical  conditions  have  been  developed  in  the  carnivora 
which  have  the  effect  of  so  slowing  the  rate  of  passage  of  food 
through  the  duodenum  that  the  time  of  exposure  of  food-stuffs  in 
the  duodenum  of  these  animals  to  the  action  of  bile  and  pancre- 
atic juice  is  greater  than  in  the  herbivora. 

From  these  facts  one  would  infer  that  it  is  of  physiological 
importance  that  the  fats  and  proteids  should  be  retarded  in  their 
passage  through  the  duodenum  in  order  that  they  niay  be  longer 
acted  upon  by  the  bile  and  pancreatic  juice  while  the  food 
yet  contains  combined  acid,  and  before  it  reaches  the  alkaline 
succus  entericus  of  the  jejunum  and  ileum.  This  physiological 
inference  finds  support  in  laboratory  experiments  which  I  have 
previously  published,  and  have  outlined  in  the  preface  to  this 
paper. 

It  is  a  well-known  fact  that  climate  may  have  considerable 
influence  in  determining  the  amount  of  fat  and  proteid  taken. 
Arctic  animals  take  much  more  fat  than  animals  of  the  same 
family  living  in  the  tropics.  In  view  of  this  fact,  it  would  be 
interesting  to  inquire  whether  a  long  residence  of  many  genera- 
tions in  a  hot  or  a  cold  climate  does,  by  reason  of  the  difference 
in  the  amount  of  fat  and  proteid  taken,  produce  a  change  in  the 
arrangement  of  the  bile  and  pancreatic  ducts  in  animals  of  the 
same  family^  despite  the  potent  influence  which  the  primitive 
type  would  have  in  maintaining  the  same  structure  under  all 
conditions.  For  example,  it  would  be  interesting  to  know 
whether  there  is  any  difference  in  the  arrangement  of  the  bile 
and  pancreatic  ducts  in  the  arctic  and  the  tropic  representatives 
of  the  dog  and  bear  families,  and  it  would  also  be  worth  while 
to  compare  the  anatomy  of  the  bile  and  pancreatic  ducts  of  the 
Esquimaux  with  that  of  human  natives  of  the  tropics.  But  for 
want  of  reliable  data  this  interesting  question,  of  the  influence 
of  climate  on  the  anatomy  of  these  ducts,  could  not.be  considered 
in  this  study. 

With  the  assistance  of  Dr.  I'rank  Southgate,  I  made  the 
measurements  in  the  following  named  animals  :  Chimpanzee, 
Jeopard,  raccoon,  Jemur,  Capuchin  monkey,  seal,  wildcat,  domes- 


B.   K.  RACHFORD.  85 

tic  cut,  Macaque  monkey,  opossum,  dog-,  rat,  ox,  sheep,  pig, 
rabbit  and  skunk. 

1  am  also  indebted  for  assistance  in  the  preparation  of  the 
tables  to  the  following  named  gentlemen  :  Dr.  Leitz,  of  Frank- 
fort-on-the-Main  ;  Prof.  A.  Tarenetsky,  of  St.  Petersburg ;  Prof. 
T.  Munk,  of  Berlin  ;   Prof.  Pietro  Albertoni,  of  Bologna. 

I  also  obtained  much  valuable  information  from  the  lectures 
of  Wm.  Henry  Flower,  published  in  the  ^fcd^cal  Times  and 
Gazette^  London,  187J,  as  well  as  from  the  works  of  Owen, 
Cuvier  and  M.  Edwards. 


Jirpriiited  from  Archives  of  Prdtatrirs,  yiinr,  7900. 


VI.— PANCREATIC  DIGESTION  OF  CASEIN.' 


In  the  following  experiments,  which  were  devised  for  the 
purpose  of  studying  certain  phases  of  the  pancreatic  digestion  of 
casein,  I  used  rabbits'  pancreatic  juice  obtained  by  the  method  I 
have  elsewhere  described."'^  Pancreatic  juice,  thus  obtained,  was 
collected  in  a  common  receptacle  and  afterward  equally  divided 
between  the  digestion  tubes  of  an  experiment,  so  that  each  tube 
might  contain  an  equal  quantity  of  pancreatic  juice  of  like  diges- 
tive capacity. 

The  bile  was  also  obtained  from  the  rabbit  and  filtered  before 
using.  The  milk  employed  was  ordinary  dairy  milk,  boiled  and 
neutralized. 

Each  digestion  tube  of  an  experiment  contained  the  same 
quantity  of  this  milk,  diluted  either  with  an  equal  quantity  of 
water  or  some  other  diluent,  as  detailed  in  the  various  experi- 
ments. 

The  digestion  tubes  were  kept  in  a  water  bath,  at  a  tempera- 
ture of  38°  C,  for  five  or  six  hours,  and  their  contents  were 
stirred  from  time  to  time  with  glass  rods  especially  prepared  for 
the  purpose.  At  the  close  of  each  experiment  the  undigested 
casein  in  each  tube  was  coagulated  by  the  addition  of  lactic  acid 
and  a  saturated  solution  of  ammonium  sulphate.  By  filtration, 
in  a  warm  chamber,  this  undigested  casein  was  received  on 
weighed  and  marked  filter  papers,  which,  after  being  thoroughly 
washed,  was  slowly  dried  and  weighed  at  a  temperature  of  100°  C. 
The  amount  of  undigested  casein  in  each  tube  was  obtained  by 
subtracting  from  the  gross  weight  thus  obtained  the  weight  of 
the  corresponding  filter  paper.  Tube  No.  1  of  each  experiment 
contained  the  same  quantity  of  milk  as  the  other  tubes,  but  did 

1  Read  before  the  American  Pediatric  Society,  Washington,  D.  C, 
May  1-3,  1900. 

2  Americau  Journal  of  Physiology,  Vol.  ii,  No.  5. 
86 


B.   K.  RACHFORD.  87 

not  contain  pancreatic  juice  or  other  ingredients  which  might 
change  the  casein.  At  the  close  of  an  experiment,  therefore, 
tube  1  contained  unchanged  casein  wiiich,  when  coagulated,  was 
used  to  determine  the  amount  of  casein  each  tube  contained  at 
the  beginning  of  the  experiment.  The  amount  of  casein  which 
had  been  converted  into  peptones  in  each  tube  was  obtained  by 
subtracting  from  the  amount  of  casein  in  tube  i  the  amount  of 
undigested  casein  in  each  of  the  subsequent  tubes. 

It  will  be  noted  that  13  cubic  centimetres  of  the  different 
specimens  of  milk  used  in  the  various  experiments  did  not  always 
contain  the  same  amount  of  casein,  and  it  is  for  this  reason  that 
the  corresponding  tubes  of  different  experiments  cannot  be  com- 
pared with  one  another.  The  comparative  accuracy,  however, 
of  the  deductions  drawn  from  a  comparison  of  the  various  tubes 

EXPERIMENT    I. TIME,   6    HOURS. 


Contents  of  Tuhes. 


Milk.  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c... 

Water.  15  c.c 

HCl  Dilute,  m.  % 

Milk,  15  c.c 

Water,  \^  c.c 

HCl  Dilute,  m.  34 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  i 

Milk,  15  c.c 

.4  per  cent.  Sol.  Sodium 
Carbonate,  15  c.c 

Milk,  15  c.c ..... 

.8  per  cent.  Sol.  Sodium 
Carbonate,  15  c.c... 

Milk,  15  c.c 

Lime  Water,  15  c.c... 


Bile. 


Pancreatic 
Juice. 
Minims.    1     Minims. 


Undigested  |    Digested 
Casein.       I     Casein. 


Tube 

Numbers. 


88 


PANCREATIC    DICESTION. 


of  an  experiment  is  assured  by  the  fact  that  the  same  quantity  of 
tlie  same  milk  was  used  in  each  tube  of  an  experiment. 

The  maltose  solution  used  in  these  experiments  was  prepared 
by  subjecting  u  mixture  of  water  and  one  of  the  Liebig  foods  to 
the  action  of  a  diastase  for  one  hour.  At  the  end  of  this  time, 
the  diastatic  ferment  was  destroyed  by  boiling  and  the  maltose 
solution  filtered  through  ordinary  filter  paper. 

JJy  the  above  method  the  preceding  and  following  experi- 
ments were  made. 


KXPKRIMENT    II. TIME,   6  HOURS. 


Pancreatic 

Contents  of  Tubes.                  Juice. 
i    Minims. 

Bile. 
Minims. 

Undigested 
Casein. 
Grams. 

Digested 
Casein. 
Grams. 

Tube 
Numbers. 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Lime  Water,  15  c.c 

Milk,  15  c.c 

Lime  Water,  15  c.c 

Milk,  15  c.c 

.4  per  cent.  Sol.  Sodium 
Carbonate,  15  c.c 

0 

5 
5 

5 

5 

0 
0 
0 
10 

0 

1. 125 
.697 
.640 

•583 
•584 

0 
.428 
.485 
•542 

■541 

I 
2 

3 
4 

5 

Milk,  15  c.c 

.4  per  cent.  Sol.  Sodium 
Carbonate,  15  c.c 


Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  %. 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  K. 


Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  i. 


Milk,  15  c.c 

2  per  cent.  Sol.  of  Milk 
Sugar,  15  c.c 


Milk,  15  c.c 

Maltose  Solution,  15  c.c. ! 

Milk,  15  c.c 

Maltose  Solution,  15  c.c.  I 


•540 


■598 


.606 


.660 


.651 


.690 


.639 


•585 


•527 


•519 


•465 


•474 


•435 


.486 


B.   K.  RACHFORD. 


89 


EXPERIMENT    III'. TIME,   5    HOURS. 


Contents  of  Tubes. 

Pancreatic 

Juice. 

Minims. 

Bile. 

Minims. 

Undigested 
Casein. 
Grams. 

Digested 
Casein. 
Grams. 

Tube 
Numbers. 

Milk,  15  c.c 

Water,  15  c.c 

0                      0 

1.039 

.581 

0 

I 

Milk,  15  c.c^ 

Water,  15  c.c 

6 

8 

.458                     2 

Milk,  15  c.c 

Water,  15  c.c 

6                  8                  .531 

•.508               3 

HCl  Dilute,  m.  y„ 

Milk,  15  c.c 

♦   -579 
•495 
.629 

Water,  it;  c.c 

HCl  Dilute,  m.  i 

Milk,  15  c.c 

Water,  15  c.c 

6 
6 

8 

.460 

•544 
.410 

4 

5 

HCl  Dilute,  m.  y^ 

6                  8 

Milk,  15  c.c 

Water,  15  c.c. 

6 

HCl  Dilute,  m.  i 

EXPERIMENT    IV. TIME,   5    HOURS. 


Contents  of  Tubes. 

Milk,  15  c.c .... 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  ic;  c.c 

HCl  Dilute,  m.  y» 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  i 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  1^ 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  i 

Milk,  15  c.c 

.4  per  cent.  Sol.  Sodium 
Carbonate,  15  c.c 


Pancreatic 

Juice. 

Minims. 


Bile. 

Minims. 


Undigested      Digested 
Casein.       '     Casein. 


Grams. 


Grams. 


1. 115 


•425 


•435 


.588 


.690 


.680 


•527 


•518  .597 

.596  .519 

.418       j      .697 


Tube 
Numbers. 


90 


PANCREATIC    DICESTIOX. 


EXPERIMENT     V. TIME,   5    HOURS. 


Contents  of  Tubes. 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  i:;  c.c 

IlCl  Dilute,  m.  y^ 

Milk,  15  c.c 

Water,  i:;  c.c 

HCl  Dilute,  m.  }a, 

Milk,  15  c.c 

Lime  Water,  15  c.c 

Milk,  15  c.c 

2  per  cent.  Sol.  of  Milk 
Sugar,  15  c.c 


EXPERIMENT    VI. TIME,    7    HOURS. 


Contents  of  Tubes. 

Milk,  20  c.c 

Water,  20  c.c 

Milk,  20  c.c... 

Water,  20  c.c 

Milk,  20  c.c 

Water,  20  c.c 

HCl  Dilute,  m.  i/g 

Milk,  20  c.c 

Water,  20  c.c 

HCl  Dilute,  m.  34 

Milk,  20  c.c 

Maltose  Solution,  20c. c 


Pancreatic 

Juice. 

Minims. 


Bile. 
Minims. 


Undigested      Digested 
Casein.       '     Casein. 
Grams.  Grams. 


1-705 
1-035 


1.005 


-905 


Tube 
Numbers 


.670 


.8x6 


.690 


r9o 


B.   K.  RACHFORD. 


91 


EXPERIMENT    VII. TIME,   5    HOURS. 


Contents  of  Tubes. 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

Milk,  15  c.c. 

Water,  1=;  c.c 

HCl  Dilute,  m.  y^ 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  y^ 

Milk,  15  c.c 

Lime  Water,  15  c.c 

Milk,  15  c.c 

Maltose  Solution,  15  c.c 


Pancreatic         pji_  Undigested      Digested 

Juice.  "  Casein.  Casein. 

Minims.    ;    Minims.  Grams.  Grams. 


Tube 
Numbers. 


1.060 

0 

.640 

.420 

■579 

.481 

.560 

.500 

.609 

•451 

•639 

.421 

EXPERIMENT    VIII. TIME,    5    HOURS. 


Contents  of  Tubes. 

Milk,  15  c.c 

Water,  15  c.c 

Milk.  15  c.c 

Water,  15  c.c 

Milk,  15  c.c 

Water,  15  c.c 

HCl  Dilute,  m.  y^ 

Milk,  15  c.c 

Water,  15  c.c \ 

HCl  Dilute,  m.  y^ 

Milk,  15  c.c    

Lime  Water,  15  c.c 

Milk,  15  c.c 

Maltose  Solution,  15  c.c. 


Pancreatic 

Juice. 

Minims. 


Bile  Undigested      Digested 

Casein.  Casein. 

Minims.  Grams.  (irams. 


1.076 
•569 
•536 

■529 

•503 
■556 


•507 

•540 

•547 

•573 
.520 


Tube 

Numbers 


92 


PANCREATIC    DIGESTTOX 


In  order  to  f;icilitate  the  study  of  the  (|iiestions  involved  in 
the  above  experiments,  I  have  by  grouping  tlie  tubes  bearing 
upon  the  same  subject,  made  a  ninnber  of  tables  which  will  now 
be  considered  under  appropriate  headings. 


[XKLUKNCE    OF    MALTOSE    ON    THE     I'ANCKEATIC    DIGESTION 
OF    CASEIN. 

Table  I. 


Contents  of  Tubes. 


Pancreatic 
Juice. 

Minims. 


Bile. 

Minims. 


Casein 

Dig^ested. 

Gram. 


Milk,  15  c.c.-j-Water,  15  c.c 

Milk,  15  cc+Maltose  Sol.,  15  c.c 

Milk,  15  c.c. -)- Water,  15  c.c 

Milk,  15  c.c.-|-Maltose  Sol.,  15  c.c 

Milk,  15  c.c.+Water,  15  c.c 

Milk,  15  c.c.-4-Maltose  Sol.,  15  c.c 

Milk,  15  c.c. -(-Water,  15  c.c 

Milk,  15  c.c.-j-Maltose  Sol.,  15  c.c 

Milk,  15  c.c. -(-Water,  15  c.c 

Milk,  15  c.c.-j-Maltose  Sol.,  15  c.c 

Milk,  15  c.c. -(-Water,  15  c.c 

Milk,  15  c.c.-j-Milk  Sugar  Sol.,  15  c.c 

Milk,  15  c.c.-^Water,  15  c.c 

Milk,  15  c.c. -(-Milk  Sugar  Sol.,  15  c.c 


10 
10 


10 
10 
10 
10 
10 
10 
10 
10 
10 


.420 
.421 

•507 
.520 
.670 
.790 

.42X 

•435 
.428 
.486 
.510 

•529 

.428 

•474 


By  a  study  of  this  table  it  will  be  noted  that  the  pancreatic 
digestion  of  casein  was  in  every  instance  slightly  facilitated  by 
the  presence  of  a  maltose  solution,  and  that  in  Experiments  VI 
and  VII  of  this  series,  a  milk  sugar  solution  seemed  to  exercise 
the  same  favorable  influence.  The  inference,  therefore,  from  this 
table  is  that  rabbits'  pancreatic  juice  in  the  presence  of  bile  is 
somewhat  assisted  in  casein  proteolysis  by  the  presence  of  a  mal- 
tose or  milk  sugar  solution. 

In  a  previous  paper  ^  I  demonstrated  the  physiological  fact 
that  acid  proteids  undergoing  digestion  will  slightly  increase  the 
diastatic  action  of  rabbits'  pancreatic  juice.  It  would  seem, 
therefore,  from  these  observations  that  the  inference  may  be 
drawn  that  both  the  diastatic  and  proteolytic  action  of  rabbits' 
pancreatic  juice  goes  on  more  rapidly  when  the  juice  is  acting 
upon  a  mixture  of  starches  and  albumens  than  when  the  juice  is 
acting  separately  upon  these  food-stuffs. 

It  must,  however,  be  remembered  that  there  are  some  difH- 

I  American  yournal  of  Physiology ,  Vol.  ii,  No.  5. 


B.   K.  RACHFORD. 


93 


culties  in  the  way  of  applying  these  principles  in  the  solution  of 
the  much  discussed  question  of  the  value  of  gruels  in  infant 
feeding. 

Jacobi  has  long  taught  that  in  healthy  children  milk  diges- 
tion goes  on  more  satisfactorily  when  it  is  mixed  with  a  decoc- 
tion of  one  of  the  cereals  ;  and  most  of  the  recent  writers  upon 
the  subject  of  children's  feeding  have  come  to  agree  with  jacobi, 
believing,  as  they  do,  that  under  the  influence  of  these  decoc- 
tions the  rennet  and  hydrochloric  acid  of  the  stomach  precipitate 
the  casein  in  more  tlocculent  clots,  thus  enabling  the  ferments  to 
come  in  more  intimate  contact  with  the  casein  to  be  digested.^ 
Whatever  may  be  the  explanation,  however,  I  think  we  may 
possibly  infer  from  the  above  experiments  that  the  favorable 
influence  of  these  cereal  decoctions  on  casein  digestion  is  con- 
tinued even  after  the  milk  leaves  the  stomach  and  comes  imder 
the  influence  of  the  various  digestive  enzymes  of  pancreatic  juice 
in  the  intestinal  canal. 


INFLUENCE     OF     LIME     WATER     ON     THE     PANCKEATIC 
DICiESTION    OF    CASEIN. 

Table  II. 


Contents  of  Tubes. 

Pancreatic 

Juice. 

Minims. 

T«:i„               Casein 
^''^-           Digested. 
Minims.         Grams. 

Milk,  15  c.c.-j-Water,  15  c.c 

Milk,  15  c.c.-^-Lime  Water,  15  c.c 

Milk,  15  c.c.-j-Water,  15  c.c 

Milk,  15  c.c.^-Lime  Water,  15  c.c 

Milk,  15  c.c.-i-Water,  15  c.c 

Milk,  15  c.c.^Lime  Water,  15  c.c 

Milk,  15  c.c.^Water,  15  c.c 

Milk,  15  c.c.-f-Lime  Water,  15  c.c 

Milk,  15  c.c.-|- Water,  15  c.c 

Milk,  15  c,c.4-Lime  Water,  15  c.c 

Milk,  15  c.c.-f  Water,  15  c.c 

Milk,  15  c.c.-j-Lime  Water,  15  c.c 

6 
6 

8 
8 
8 
8 
8 
8 

0                    .554 
0                    .652 
10                  .428 
0                    .405 
10                  .428 
10                  .542 
10                  .510 
10                  .375 
10                  .42<t 

10            .451 
10               .507 

10          .573 

A  study  of  this  table  indicates  that  lime  water  slightlv  in- 
creases the  proteolytic  action  of  rabbits'  pancreatic  juice  on  casein. 
The  important  role  wiiich  lime  water  has  long  played  in  the  milk 
feeding  of  infants  has  given  it,  in  certain  conditions,  an  empirical 
value  which  cannot  be  doubted.  It  is  perhaps  true  that  the  bene- 
ficial  results   which  are  obtained   from  the  use  of   lime   water,  in 

I   Chapin.  Archires  of  Pediatrics,  December,  1899. 


94 


PANCREATIC    DIGESTION. 


the  gastric  digestion  of  milk,  are  in  part  due,  as  Dr.  Chapin  said 
in  a  paper  before  this  Society  last  year,  to  the  fact  that  the  action 
of  rennet  is  facilitated  by  the  presence  of  the  salts  of  lime.  It 
also,  however,  has  some  value  in  neutralizing  the  acidity  which 
has  almost  always  developed  in  dairy  milk  before  it  has  reached 
the  dwelling  houses  in  our  large  cities.  And  may  it  not  also  be 
possible  that  the  beneficial  influence  of  lime  water  on  the  pan- 
creatic digestion  of  casein  is  exerted  in  somewhat  the  same  way? 
That  is  to  say,  in  the  milk  feeding  of  infants  the  lime  water,  by 
facilitating  the  Haky  deposit  of  casein  in  the  stomach,  causes  the 
casein  to  come  into  the  presence  of  the  pancreatic  juice  in  a  more 
suitable  form  for  active  proteolysis,  and  it  may  even  be  conceived 
that  the  lime  salts  themselves  may  reach  the  intestine,  there  to 
stimulate  the  pancreatic  digestion  of  casein. 


INKLUKNCE    OF    SODIUM    CARBONATE    ON    THE     FANCKKATIC 
DIGESTION     OF    CASEIN. 

Table  III. 


Contents  of  Tubes. 


Pancreatic 

Juice. 

Minims. 


Milk,  15  c.c.-)-Water.  15  c.c 

Milk,  15  C.C.4-.4  per  cent.  Sod.  Carb 

Sol.,  15  c.c 

Milk,  15  c.c.^-Water,  15  c. 

Milk,  rf  C.C.4--4  per  cent.  Sod.  Carb 

Sol.,  15  C.C 

Milk,  15  c.c.4-Water,  15  c.c 

Milk,  15  c.c.-)-.4  per  cent.  Sod.  Carb 

Sol.,  15  c.c 

Milk,  15  c.c.^Water,  15  c.c 

Milk,  15  c.c.-f--4  per  cent.  Sod.  Carb 

Sol.,  15  c.c 

Milk,  15  c,c.-]-Water,  15  c.c 

Milk,  15  c.c.-|-.8  per  cent.  Sod.  Carb 

Sol.,  15  c.c 


10 

6 


Bile. 
Minims. 


10 
O 


Casein 

Digested. 

Grams. 


•.=^54 

.642 

.428 

•54' 

.428 

.585 
.690 

.697 

•554 

•653 


The  study  of  this  table  shows  that  the  presence  of  sodium 
carbonate  greatly  increases  the  proteolytic  action  of  rabbits'  pan- 
creatic juice  on  casein.  This  physiological  observation  is  of  im- 
portance because  of  the  fact  that  sodium  carbonate  is  a  normal 
constituent  of  the  succus  entericus.  One  may  infer,  therefore, 
that  the  alkaline  intestinal  juice  will  facilitate  the  action  of  trypsin 
on  casein.  One  cannot,  however,  say  that  the  value  of  sodium 
carbonate  in  the  milk  feeding  of  children  depends  either  wholly 


B.   K.  RACHFORD. 


95 


or  partly  upon  this  physiological  fact,  since  it  is  quite  i!npt)ssible 
to  see  how  sodium  carbonate  could  pass  through  the  acid  con- 
tents of  the  stomach  and  reach  the  intestinal  canal  in  a  condition 
to  facilitate  the  pancreatic  digestion  of  casein.  The  good  that 
comes  from  sodium  carbonate  in  infant  feeding  is  probably  due 
to  the  fact  that  it  neutralizes  the  fermentation  acids  which  have 
been  formed  in  the  milk. 


INFLUENCE    OF    COMBINED    II VDllOCHLORIC    ACID    ON    THE 
PANCREATIC    DIGESTION    OF    CASEIN. 

Tahle   IV. 


Contents  of  Tubes. 


Milk,  15  c.c.-|-Water,  15  c.c 

Milk,  15  c.c.-|-Water,  15  c.c 

Milk,  15  c.c.-|- Water,  15  c.c 

Milk.  15  c.c.-)-Water,  15  c.c 

Milk,  15  c.c. -[-Water,  15  c.c 

Milk,  15  c.c.-j-Water,  15  c.c 

Milk,  15  c.c. -[-Water,  15  c.c 

Milk,  15  c.c.-|-Water,  15  c.c 


Pancreatic 

Juice. 

Minims. 


10 
10 
10 


10 
10 


HCl 
Dilute. 
Minims. 


O 


Casein 

Digested,  i 

Grams. 


.690 

.680 
.690 

•  597 
.690 

•,^-7 
.690 

■519 


The  few  experiments  recorded  in  this  table  indicate  that  com- 
bii,ied  hydrochloric  acid  slightly  retards  the  proteolytic  action  of 
trypsin  on  casein.  The  retarding  influence,  however,  is  not  very 
great,  with  the  amount  of  acid  here  used,  considerable  proteolysis 
being  accomplished  by  the  pancreatic  juice  when  one  minim  of 
dilute  hydrochloric  acid  was  added  to  fifteen  cubic  centimetres 
of  milk. 

If  one  refers  to  Experiment  I  in  connection  with  the  study  of 
the  following  table,  it  is  evident  that  bile  not  only  neutralizes 
the  retarding  influence  of  combined  hydrochloric  acid  on  the 
pancreatic  digestion  of  casein,  but  that  by  its  presence  it  enables 
the  pancreatic  juice  to  do  more  work  on  acid  casein  than  it  could 
do  on  neutral  casein,  or  on  neutral  casein  mixed  with  bile.  That 
is  to  say,  bile  assists  the  pancreatic  juice  in  the  digestion  of 
casein,  but  it  renders  even  greater  assistance  when  the  casein 
is  partly  saturated  with  hydrochloric  acid.  When,  therefore, 
rabbits'  bile  and  rabbits'  pancreatic  juice  are  brought  in  contact 
with  acid  casein,  conditions  are  provided  ^vhich  favor  the  proteo- 
lytic action  of  trypsin  on  casein. 


96 


PANCREATIC    DIGESTION. 


INFLUENCE    OK     HII.E    AND    COMBINED    IIVDKOCHLORIC    ACID    ON 
TlIK     PANCREATIC    DIGESTION    OF    CASEIN. 

Table  V. 


Contents  of  Tubes. 


Pancreatic 
Juice. 
Minims.        Minims. 


Bile. 


HCl 

Dilute. 
Minims. 


Milk, 

^?> 

c.c. -(-Water 

,  IS 

c.c 

6 

12 

.Milk, 

iq 

c.c. — Water 

li; 

c.c 

6 

12 

Milk, 

i; 

c.c.-|-Water 

i^ 

c.c 

6 

12 

Milk, 

i^ 

o.c.-|- Water 

i^ 

c.c 

6 

12 

Milk, 

IS 

c.c. — Water 

i^ 

c.c 

^ 

10 

Milk, 

i^ 

c.c. — Water 

r:; 

c.c 

^ 

10 

Milk, 

i^ 

cc+Water 

Is 

c.c 

s 

10 

Milk, 

i^ 

c.c. -(-Water 

Is 

c.c 

s 

10 

Milk, 

i^ 

c.c. -(-Water 

Is 

6 

8 

Milk, 

m 

c.c. -(-Water 

m 

c.c 

6 

8 

Milk, 

i,^ 

c.c. -(-Water 

Is 

c.c 

6 

8 

Milk, 

1=; 

c.c. -(-Water 

Is 

c.c 

6 

8 

Milk, 

i,S 

c.c. -(-Water 

IS 

c.c 

8 

10 

Milk, 

i.s 

c.c. -(-Water 

IS 

c.c 

8 

10 

Milk, 

i,^ 

c.c. -(-Water 

I^ 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water 

I  > 

c.c 

8 

10 

Milk, 

m 

c.c. — Water 

Is 

c.c 

8 

10 

Milk, 

IS 

c.c. — Water 

I  s 

c.c 

8 

10 

Milk, 

IS 

c.c. — Water, 

Is 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water, 

I^ 

c.c 

8 

10 

Milk, 

1=; 

c.c. -(-Water 

Is 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water, 

1=; 

c.c 

8 

10 

Milk, 

i^ 

c.c. -(-Water, 

IS 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water, 

IS 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water, 

IS 

c.c 

8 

10 

Milk, 

IS 

c.c. -(-Water, 

IS 

c.c 

8 

10 

Milk, 

m 

c.c. -(-Water, 

IS 

c.c 

8 

10 

Milk, 

IS 

c.c.^^Water, 

IS 

c.c 

8 

10 

Milk, 

1=; 

c.c. -(-Water, 

Is 

c.c 

6 

12 

Milk, 

IS 

c.c. 4- Water, 

m 

c.c 

6 

12 

Milk, 

li; 

c.c. — Water, 

IS 

c.c 

s 

i« 

Milk, 

IS 

c.c. -{-Water, 

1=; 

c.c 

^ 

10 

Milk. 

IS 

c.c. -(-Water, 

IS 

c.c 

6 

8 

Milk, 

1=; 

c.c. -(-Water, 

IS 

c.c 

6 

8 

Milk, 

15 

c.c.4-Water, 

IS 

c.c 

6 

8 

Milk, 

15 

c.c.-j-Water, 

15 

c.c i 

6 

8 

Casein 

Digested. 

Grams. 


.581 

■594 

.S8i 

■590 
.428 

•527 
.428 

■S19 

.4t;8 
.S08 
•458 
•544 

.sIO 

•  57" 

.sIU 

.s98 
.670 
.691) 
.670 
.816 
.420 
.481 
.420 

.sOO 
.507. 

■  54" 

■  .=^07 

■  547 

•584 
•567 
.428 
.46s 
.458 
.460 

•45« 
.410 


This  table  shows  that  the  addition  of  a  small  percentage  of 
hydrochloric  acid  almost  invariably  increases  the  proteolytic 
action  of  pancreatic  juice  upon  casein,  when  the  juice  is  acting 
in  the  presence  of  bile.  And  when  one  remembers  that  in  the 
carnivora  the  duodenal  contents  are  always  acid,  and  that  even 
in  the  herbivora  a  certain  amount  of  hydrochloric  acid  is  com- 
bined with  the  proteids  as  they  are  discharged  from  the  stomach 
into  the  duodenum,   and    that  the   intestinal  contents   lose  their 


B.  K.  RACHFORD. 


97 


acidity  and  become  alkaline  in  their  reaction,  only  after  they 
have  passed  down  some  distance  from  the  pylorus  (in  the  carnivora 
a  longer  distance  than  in  the  herbivora),  then  one  can  see  the 
force  of  the  above  physiological  propositions  in  explaining  the 
digestion  of  milk  in  the  intestinal  canal  of  all  animals,  including 
man.  In  the  infant  of  the  human  species,  for  example,  let  us 
suppose  that  the  milk,  after  being  subjected  in  the  stomach  to  the 
influence  of  rennet,  hydrochloric  acid  and  pepsin,  is  discharged, 
partially  digested,  through  the  pylorus,  into  the  duodenum  ;  the 
casein  being  either  wholly  or  partly  saturated  with  hydrochloric 
acid  is  brought  at  once  under  the  influence  of  a  mixture  of  bile 
and  pancreatic  juice,  and  these  conditions,  as  we  have  demon- 
strated, being  m.ost  favorable  to  the  pancreatic  digestion  of  casein, 
proteolysis  will  go  on  rapidly.  As  the  casein  passes  down  the 
intestinal  canal,  it  presently  finds  itself  in  an  alkaline  medium, 
the  combined  hydrochloric  acid  being  wholly  neutralized  by  the 
sodium  carbonate  arid  other  alkalies  found  in  the  intestinal  juices. 
In  this  alkaline  medium,  as  we  demonstrated  in  Table  III,  the 
trypsin  still  finds  itself  under  conditions  most  favorable  to  its 
action,  and  proteolysis  thus  continues  under  favorable  influences 
throughout  the  intestinal  canal. 

That  a  small  amount  of  combined  hydrochloric  acid  will,  in 
the  presence  of  bile,  actually  assist  the  proteolytic  action  of  pan- 
creatic juice  on  casein,  is  a  physiological  fact  which  has  some 
bearing  on  the  feeding  of  sick  infants. 

Jacobi,  in  speaking  of  infant  feeding,  says:  "In  acute  and 
debilitating  diseases  which  furnish  no,  or  little,  hydrochloric  acid 
in  the  gastric  secretion,  a  small  quantity  of  the  latter,  well  diluted, 
must  be  provided  for."  This  is  but  one  of  many  expressions 
I  find,  noting  the  value  of  hydrochloric  acid  in  the  feeding  of 
sick  children.  In  recent  years  my  own  clinical  experience  has 
taught  me  that  hydrochloric  acid  is  one  of  the  most  valuable 
agents  we  have  in  the  treatment  of  diseases  marked  by  feeble 
digestion  in  infants.  Hydrochloric  acid  is,  I  believe,  of  special 
value,  as  Jacobi  says,  in  those  cases  where  malnutrition  is  pro- 
nounced, and  the  hydrochloric  acid  of  the  gastric  juice  is  for  this 
reason  deficient.  I  have  found  it  of  value,  however,  in  almost 
all  cases  where  there  is  deficient  casein  digestion,  as  manifested 
by  curds  in  the  stools.  Casein  dilution,  as  Rotch  has  so  clearly 
demonstrated,  is  the  rational  treatment  of  this  condition.     Yet 


98  PANCREATIC    DIGESTION. 

if  we  are  to  look  to  the  proper  nutrition  of  the  infant,  there  is  a 
limit  to  the  amount  of  dilution  which  may  be  resorted  to.  In 
these  cases  I  have  often  obtained  the  greatest  benefit  from  the 
use  of  a  pepsin  hydrochloric  acid  solution.  In  my  hospital  wards 
I  have  used  this  mixture  with  great  satisfaction  in  infants  suffer- 
ing from  casein  indigestion,  due  wholly  or  partly  to  a  general 
malnutrition.  These  cases,  as  a  rule,  respond  quickly  to  the  acid, 
the  curds  diminish  or  disappear  from  the  stool,  and  the  infant  is 
able  to  take  and  digest  inore  milk.  I  wish,  however,  especially 
to  note  that  the  good  effects  of  hydrochloric  acid  are  not  limited 
to  these  cases  of  malnutrition,  but  that  it  is  also  of  real  value  in 
almost  all  cases  of  casein  indigestion,  whatever  may  be  the  cause, 
and  whether  the  infant  is  being  fed  on  breast  milk,  or  some  dilu- 
tion of  cow's  milk. 

In  the  light  of  the  above  experiments  we  can  see  that  the 
beneficial  action  of  hydrochloric  acid  is  not  confined  to  the 
stomach,  but  as  combined  hydrochloric  acid  it  is  continued  in 
the  intestinal  canal,  where  it  not  only  aids  the  pancreatic  diges- 
tion of  casein,  but  also  acts  as  an  intestinal  antiseptic.  It  is  my 
belief  that  a  small  portion  of  hydrochloric  acid  combined  with 
proteids  will,  under  certain  conditions,  aid  the  action  of  the 
enzymes  of  pancreatic  juice,  while  at  the  same  time  it  exercises 
a  restraining  influence  on  fermentations  carried  on  by  organized 
ferments. 

In  closing  this  paper  I  wish  to  add  a  note  on  certain  changes 
which  take  place  in  the  cream  of  milk  when  subjected  to  the 
combined  influence  of  bile  and  pancreatic  juice. 

In  the  experiments  above  recorded  I  noted  at  the  close  of 
certain  experiments,  that  free  fat,  or  butter,  was  found  floating 
on  the  surface  of  all  those  digestive  mixtures,  in  which  the  milk 
had  been  subjected  to  the  action  of  both  bile  and  pancreatic  juice. 
In  other  words,  it  was  noted  that  the  physiological  emulsion  of 
fats,  as  it  occurs  in  milk,  was  partially  destroyed  by  the  com- 
bined action  of  bile  and  pancreatic  juice,  but  that  this  emulsion 
was  not  destroyed  by  the  action  of  either  one  of  these  agents 
when  acting  alone.  This  observation  suggests  the  possibility 
that  the  emulsion  of  fats  in  milk  is  wholly  or  partially  destroyed 
by  the  action  of  bile  and  pancreatic  juice  in  the  intestinal  canal 
prior  to  their  absorption.  If  it  be  true  that  the  milk  emulsion  is 
destroyed  in  the  intestinal  canal,  and  the   fats  set  free,  we  can 


B.  K.  RACHFORD. 


99 


readily  understand  how  in  certain  diseases  of  the  intestinal  canal, 
which  interfere  with  the  absorption  of  foods,  we  may  have,  even 
in  milk-fed  infants,  greasy  or  fatty  stools. 

I  wish  again  in  this  paper,  as  I  have  in  previous  ones,  to 
acknowledge  the  skillful  assistance  of  Dr.  F.  A.  Southgate.  I 
am  also  indebted  to  Dr.  Dudley  Webb  for  valuable  assistance. 


Date  Due 

i,      i'd.'^'i. 

$) 

QP195  Rll 

Rachford 
J  ] --  Studies  in  pancrQatio  digestion 


